(Journal of Leukocyte Biology. 2002;71:1-8.)
© 2002
by Society for Leukocyte Biology
IL-17: prototype member of an emerging cytokine family
Sudeepta Aggarwal and
Austin L. Gurney
Department of Molecular Biology, Genentech Inc., South San Francisco, California
Correspondence: Austin L. Gurney, Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990. E-mail: nico{at}gene.com
 |
ABSTRACT
|
|---|
IL-17 is a potent proinflammatory cytokine produced by activated memory
T cells. The large-scale sequencing of the human and other vertebrate
genomes has revealed the presence of additional genes encoding proteins
clearly related to IL-17, thus defining a new family of cytokines.
There are at least six members of the IL-17 family in humans and in
mice. Initial characterization suggests that like IL-17, several of
these newly identified molecules have the ability to modulate immune
function. Neither the IL-17 family nor the cognate receptors that have
been identified for these molecules bear obvious sequence similarity to
other known families of proteins. Thus, they represent a distinct
signaling system that appears to have been highly conserved across
vertebrate evolution. The potent inflammatory actions that have been
identified for several of these factors and the emerging associations
with major human diseases suggest that these proteins may have
significant roles in inflammatory processes.
Key Words: GM-CSF • TNF-
• MAPK • JNK • pathogen
|
DISCOVERY OF THE INTERLEUKIN-17 FAMILY
|
|---|
Interleukin-17 (IL-17) was first identified as a rodent cDNA
transcript, termed CTLA8, isolated from an activated T-cell hybridoma
[1
]. It bore a striking 58% identity to a predicted
open-reading frame, HSVS13, in the T-lymphotropic herpesvirus
Herpesvirus samiri [2
]. Initial
characterization recognized that this factor could promote the
production of other cytokines and chemokines such as IL-6, IL-8, and
granulocyte colony-stimulating factor (G-CSF) from a variety of
epithelial, endothelial, and fibroblastic cell types and led to its
proposed nomenclature as an IL [2
3
4
]. IL-17 was
striking in its uniqueness. It bore no resemblance to other known ILs,
and moreover, beyond the viral ortholog, it bore no clear resemblance
to any known protein or structural domain. Its uniqueness was further
exemplified by the isolation of a receptor that binds IL-17 and is
required for signaling [2
]. IL-17 receptor (IL-17R) was
not recognized to be related to any of the other known cytokine
receptors, and remarkably, in spite of a relatively large size of 860
amino acids, it also did not possess similarity to any other known
protein nor any recognizable domains. Thus, the IL-17 system appeared
to be a distinct and potent signaling system involved in the control of
the immune response.
The recent large-scale sequencing of expressed sequence tags (est) and
genomes of several vertebrate species has led to the identification of
additional genes that bear clear homology to IL-17 and thus define an
emerging cytokine family [5
6
7
8
9
]. There are at least six
members of the family in the human genome (Fig. 1
). IL-17B and IL-17C were identified based on est, and a fourth
member, as yet unpublished but provisionally termed IL-17D, is also
relatively abundantly represented in est databases (unpublished
results). A fifth member of the IL-17 family, IL-17E, was first
discovered in human genomic sequence [6
]. The sixth
known member of the family, IL-17F, is located adjacent to IL-17 in
human genomic sequence [8
]. Comparison of the human
IL-17s with other species suggests that IL-17 family members are highly
conserved across vertebrate evolution. In contrast, clear orthologs
have not been identified in Drosophila or
Caenorhabditis elegans. The IL-17s are all similarly sized,
secreted proteins of 150–180 amino acids. They bear greatest
similarity within the C-terminal 70 amino acids. Although there is not
a strict conservation of spacing, there are four well-conserved
cysteines and at least two additional cysteines that appear likely to
be functionally conserved but with more variable spacing. Members of
the IL-17 family are all expressed as dimers, and with the exception of
IL-17B, they are covalent dimers (unpublished results). Recent
structural analysis has revealed the unexpected finding that IL-17F
and, therefore likely, the other IL-17s adopt a cysteine knot
conformation [8
].
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Figure 1. Sequence of IL-17 family members. Shown is a sequence alignment of the
six known human IL-17 family members. Identical residues are boxed, and
conserved cysteines are indicated by bullets.
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|
BIOLOGICAL ACTIONS OF IL-17 AND FAMILY MEMBERS
|
|---|
The biological actions of IL-17 are quite proinflammatory in
character. It increases the local production of chemokines such as IL-8
[10
11
12
], monocyte chemoattractant protein-1 (MCP-1)
[13
, 14
], and Gro [15
],
thereby promoting the recruitment of monocytes and neutrophils
[16
17
18
]. Further, it stimulates the production of the
hematopoietic cytokines G-CSF and granulocyte macrophage (GM)-CSF that
promote the expansion of these myeloid lineages
[19
20
21
]. Other actions such as the stimulation of IL-6
and PGE2 production enhance the local inflammatory environment
[4
, 22
23
24
]. In addition, IL-17 also drives
T-cell responses, notably through the induction of the costimulatory
molecule intercellular adhesion molecule (ICAM)
[25
26
27
].
IL-17 has long been considered a molecule produced by activated memory
T cells [1
]. Studies designed to establish whether IL-17
could be classified according to the Th1/Th2 paradigm have been unable
to provide clear categorization [28
29
30
]. Although
individual T-cell clones can be derived, which produce interferon-
(IFN-) and IL-17, many IL-17-producing clones appear to produce
neither IFN- nor IL-4. The significance of the observation that
IL-17 was produced by activated CD4+CD45RO memory T cells
has perhaps not been fully appreciated. One interpretation of this
observation is that there exists within the memory T-cell compartment a
population of T cells that were originally activated by unknown stimuli
to produce IL-17. Having acquired this differentiated, polarized state,
these cells are able to re-express IL-17 when subsequently restimulated
with relatively nonspecific stimuli such as phorbol 12-myristate
13-acetate (PMA) and ionomycin. This interpretation has been given
strong support by the recent observation that splenocytes from T-cell
receptor (TCR) transgenic mice could be driven to produce IL-17 when
primed with cognate peptide in the presence of microbial lipopeptides
[31
]. The study demonstrated that this outcome was not
observed when cells were stimulated with peptide and the known Th1
driver IL-12 [32
, 33
]. Characterization of
the cytokine expression profile of individual T cells within the
population by cytometric single-cell analysis revealed that the
IL-17-expressing cells represent a distinct population from the
traditional Th1 profile [34
35
36
] and are characterized
by the production of IL-17, GM-CSF, and tumor necrosis factor
(TNF-). This represents the first known physiological stimuli
capable of directing the development of IL-17-expressing T cells. These
data fit well with other observations that there is abundant IL-17 in
various conditions that are impacted by microbial pathogens, including
Helicobacter pylori-infected gastric mucosa
[37
] and synovial fluid of patients with Lyme arthritis
[31
].
Taken together, these data suggest a new paradigm for the consideration
of IL-17 within the immune system. IL-17 may serve to mediate an
adaptive immune response to pathogens that is characterized by a heavy
reliance on cells thought to function primarily as mediators of the
innate immune response. Thus, the immune system is able, by virtue of
this memory T-cell response, to promote a more rapid recruitment of
monocytes and neutrophils through IL-17-induced chemokine production
[10
11
12
13
14
15
, 38
, 39
]. Further, it
is able to promptly begin to stimulate the production of additional
myeloid cells through the production of GM-CSF by the activated
IL-17/GM-CSF/TNF-producing T cells [31
] and additional
GM-CSF and G-CSF production from local IL-17-stimulated stromal cells
[21
22
23
24
]. However, the induction of ICAM by IL-17 acts
to promote further T-cell responses, indicating the character of this
adaptive response is not an exclusive reliance on phagocytic cells of
the myeloid lineage.
The new IL-17s each appear to have very distinct expression patterns
and therefore likely have distinct biological roles. The expression of
IL-17 itself is very highly regulated, and IL-17 transcripts are
essentially undetectable other than in select, activated T cells
[11
]. IL-17B is moderately expressed in several
peripheral tissues as well as immune tissues [5
,
7
]. IL-17C was found to be quite rare, but like IL-17,
its expression is highly regulated in inflammatory conditions
(unpublished results). The expression of the unpublished molecule, here
termed IL-17D, appears to be particularly high in skeletal muscle and
the nervous system, suggesting its biology is likely to be quite
different from IL-17. The expression of IL-17E is strikingly low but
can be detected by polymerase chain reaction (PCR) in various
peripheral tissues [6
]. IL-17F mRNA expression seems
most similar to IL-17, with expression generally very low, but clearly
detectable in activated populations of T cells [8
,
9
]. Of these new members of the IL-17 family, IL-17E and
IL-17F are currently the best characterized and so will be described in
greater detail.
IL-17E has potent inflammatory effects in vitro and in vivo. Initial
characterization of IL-17E indicated that it, analogous to IL-17, was
able to stimulate activation of nuclear factor 
B (NF-B), a
transcription factor that contributes to the signal transduction of
several important proinflammatory molecules including TNF, IL-1ß, and
Toll-related receptors [40
41
42
]. Consistent with this,
it was shown to induce production of IL-8, a downstream target of each
of these signaling pathways. Recently, the action of IL-17E has been
characterized in the transgenic mouse setting [43
].
Overexpression of IL-17E resulted in profound alterations of the immune
system. Several features of the response had Th 2-like character
[44
, 45
]. The mice displayed eosinophilia
and increased serum immunoglobulin (Ig)E and IgG1 but not IgG2a. Serum
levels of IL-13 and IL-5 were elevated. Further, elevated gene
expression of several Th2 cytokines, including IL-4, IL-5, IL-10, and
IL-13, was observed in multiple tissues. However, although the systemic
response had Th2-like aspects, there were markedly different
tissue-specific expression patterns of cytokines, chemokines, and
adhesion molecules. For instance, high levels of TNF and ICAM were
expressed in liver. Elevated levels of G-CSF were expressed in several
tissues and likely contributed to the substantial neutrophilia
displayed in these mice. Moreover, exposure to IL-17E induced
pathological changes in multiple tissues, particularly liver, heart,
and lung, characterized by mixed inflammatory cell infiltration,
epithelial hyperplasia, and hypertrophy. Thus, IL-17E appears to be a
unique pleiotrophic cytokine that engages a systemic Th 2-like response
with tissue-specific immunological and pathological changes.
The gene encoding human IL-17F is located adjacent to IL-17 (human
genomic sequence in clone RP11-935B23; Genbank accession AL355513)
[8
]. IL-17 and IL-17F share 44% amino acid identity,
whereas the other members of the IL-17 family share a more limited
15–27% amino acid identity, suggesting that IL-17A and IL-17F form a
distinct subgroup within the IL-17 family. As mentioned above, IL-17F
is produced by activated T cells. Whether this expression is in
precisely the same population of cells that express IL-17 and whether
there are differences in the stimuli that induce their expression are
unresolved questions. IL-17F has also been demonstrated in activated
monocytes [9
]. IL-17F appears to have similar biological
actions as IL-17 [8
] and is able to promote the
production of IL-6, IL-8, and G-CSF from a wide variety of cells.
Similar to IL-17, it is able to induce cartilage matrix release and
inhibit new cartilage matrix synthesis. Thus, like IL-17, IL-17F may
potentially contribute to the pathology of inflammatory disorders such
as rheumatoid arthritis (RA) [46
47
48
49
50
]. IL-17F has also
been shown to induce transforming growth factor-ß (TGF-ß)
expression in human umbilical vein endothelial cells and decrease their
ability to undergo capillary tube formation, suggesting a potential
ability to inhibit angiogenesis [9
].
|
STRUCTURE OF THE IL-17s
|
|---|
The apparent uniqueness of the sequences of IL-17 and its receptor
has made it difficult to appreciate whether the IL-17 system is truly
unrelated to other known signaling systems. Although it has not been
possible to identify orthologs of these molecules outside of the
vertebrates, they have the ability to engage components of the NF-B
and mitogen-activated protein kinase (MAPK) signaling pathways
[2
, 5
, 6
, 51
,
52
] and thus use signaling systems that are broadly
distributed across metazoan evolution [53
]. To better
understand the character of the IL-17s, the crystal structure of one of
the family members, IL-17F, has been determined recently
[8
]. Unexpectedly, the structure of IL-17F reveals that
the protein adopts a cysteine knot fold and suggests that the family
may have a relationship to the cysteine knot superfamily of proteins
[54
, 55
]. IL-17F folds in a manner quite
similar to that of nerve growth factor (NGF) [56
] and
the other neurotrophins [57
]. In addition, IL-17F and
NGF exist as dimers. The IL-17 family does not have any appreciable
sequence identity with the neurotrophins. The cysteine knot superfamily
is a diverse family and includes other proteins, such as the endocrine
glycoprotein hormones (e.g., chorionic gonadotropin), the
platelet-derived growth factors (PDGFs), and the TGF-ß family, which
also display limited sequence similarity [54
]. Although
IL-17 folds in a manner highly analogous to the cysteine knot
superfamily, one of the cononical cysteine pairs, the pair that links
through the ring formed by the other two pairs and thereby forms the
"knot," is not present. Instead, a third cysteine bridge is formed
by a spatially distinct pair of cysteines. Thus, although the members
of IL-17 family clearly adopt a cysteine knot fold, actual evolutionary
membership within the family cannot be assumed.
The tertiary structural similarity between the IL-17s and the
neurotrophins raises some interesting speculations. The neurotrophins
bind to two classes of receptors [58
59
60
61
], the Trk
tyrosine kinases and p75NTR, a member of the TNF receptor
superfamily. Neither the Ig domains within the extracellular domains of
the Trk receptors nor the cysteine-rich extracellular domains that
characterize membership in the TNF receptor family bear obvious
similarity to the IL-17R. However, TNF has clear similarities to IL-17
in its ability to modulate immune function and promote an inflammatory
response [40
]. Another interesting speculation relates
to the Drosophila protein späztle [62
,
63
], which has been predicted to adopt a neurotrophin
fold [64
] and has been shown genetically to be an
endogenous ligand for the Drosophila Toll receptor
[65
, 66
]. The Toll receptors are members of
the leucine-rich repeat superfamily of proteins [67
68
69
70
]
and are clearly not related to the IL-17Rs. Nonetheless, it is possible
that the IL-17 system may in some manner relate to this ancient, innate
immune system.
|
IL-17R
|
|---|
Following the isolation of mouse [3
,
71
], rat [1
], human [4
,
28
], and viral [1
] homologs of IL-17,
viral IL-17 was used to identify a mouse IL-17R that bound to all
ortholog forms [2
, 72
]. In contrast to
relatively restricted expression of IL-17 [1
,
2
], IL-17R was found to be ubiquitously expressed in all
cell types examined [2
, 10
]. The mouse
IL-17R is a type 1 membrane protein that contains 864 amino acids and
eight putative N-linked glycosylation sites. The human
homolog of mouse receptor exhibits 69% sequence homology. Direct
binding assays using 125I-labeled human (h)IL-17 on cells
transfected with IL-17R have indicated that IL-17 binds to its receptor
with relatively low affinity with a Ka
value of approximately 2 x 107–2 x
108 M-1 [72
]. This
is a substantially low affinity for IL-17R, considering the low
concentrations of IL-17 required for its biological activity,
suggesting the potential presence of additional components of the
IL-17R. However, in human fibroblast cell line HFF, an antibody to
IL-17R blocks IL-6 production in response to IL-17.Fc ligand,
indicating that binding to its receptor is necessary to generate an
IL-17-specific response in these cells [72
]. Initial
studies of the new members of the IL-17 family suggest that they will
use distinct, cognate receptors. IL-17E has been identified as a
high-affinity ligand for a newly recognized receptor termed IL-17Rh1
[6
] (also termed EVI27 and IL-17BR) [7
,
73
]. This receptor has also been suggested to interact
with IL-17B although apparently with lower affinity. Comparison of
IL-17R and IL-17Rh1 reveals conservation of several cysteines within
the extracellular domains, suggesting they share similar structures.
There are also conserved elements within the intracellular domain,
suggesting that these receptors likely engage similar intracellular
machinery. This is supported by the observation that IL-17E, like
IL-17, is able to induce the activity of NF-B and similar downstream
effector molecules. IL-17Rh1 was first shown as EVI27, a protein
encoded whose expression was up-regulated as a result of retroviral
integration in BXH2 murine myeloid leukemias [73
].
IL-17F, which has similar activity to IL-17, also appears able to
interact with the IL-17R (unpublished results), although the low
affinity of this interaction makes it clear that additional components
remain to be identified.
|
IL-17 SIGNALING
|
|---|
IL-17 is produced by activated T cells and mediates its
proinflammatory effects via its receptor, IL17R, which is ubiquitously
expressed on all cell types. However, the exact mechanisms of IL-17
signaling are still not fully elucidated. In chronic diseases including
RA, IL-17 results in tissue damage, directly by matrix degradation
[74
75
76
77
] or indirectly by recruiting activated
inflammatory cells and inducing other proinflammatory cytokines
including IL-1ß and TNF- to the inflamed tissue
[51
]. The matrix degradation results from up-regulation
of inducible nitric oxide synthase (iNOS) and NO in chondrocytes
through a tyrosine kinase-dependent cascade, which is protein kinase A
(PKA)- and, to a lesser extent, protein kinase C (PKC)-dependent
[75
, 78
]. IL-17 activates all three
subgroups of MAPKs, which are the p44 and p42 extracellular
signal-regulated kinases (ERK1 and ERK2), stress-induced Jun
NH2-terminal kinases (JNK), and p38 [52
,
75
, 79
, 80
]. The IL-17-induced
activation of JNKs (JNK1 and JNK2) results in up-regulation of iNOS and
cyclooxygenase-2 (COX-2) genes [75
]. NF-B activation
by IL-17 was seen in human fibroblasts [4
,
28
], intestinal epithelial cells [52
], and
chondrocyte cultures [75
, 78
]. The
mechanisms by which IL-17 activates NF-B are not resolved but appear
to be dependent on TNF receptor-associated factor (TRAF)-6
[52
, 81
].
IL-17 has also been postulated to be a major vehicle by which T cells
can communicate with the hematopoietic system [82
]. For
example, fibroblasts cultured with IL-17 were shown to support the
growth of human CD34+ hematopoietic progenitor cells and
direct their maturation toward neutrophils [4
]. More
recently, it was shown that adenovirus-mediated gene transfer of murine
IL-17 cDNA targeted to the liver stimulates granulopoiesis in mice
[83
]. In the hematopoietic system, using human monocytic
leukemia cell line U937, IL-17 was shown to trigger tyrosine
phosphorylation of several members of the Janus kinase (JAK)
and signal transducer and activator of transcription (STAT)
pathways [84
]. These included Tyk2, JAK1, -2, and –3,
and STAT 1, 2, 3, and 4, suggesting the possibility that the JAK/STAT
pathway may be involved in mediating biological effects of IL-17.
Recently, we have shown that another member of IL-17 family, IL-17E,
also activates NF-B [6
]. Furthermore, IL-17E and
recently characterized IL-17F [8
] promote the production
IL-8 and IL-6 in vitro from responsive cell lines, activities shared
with IL-17 and suggesting that the members of this family are capable
of engaging similar intracellular machinery.
|
IL-17 IN DISEASE
|
|---|
IL-17 and RA
RA is characterized by chronic inflammation as well as progressive
destruction of RA synovium and destruction of bone and cartilage
[85
]. In RA, T cells infiltrate into synovial membrane,
and tissue pathogenesis occurs through a complex cell-cell interaction
among T cells, antigen-presenting cells, endothelial cells, and
synovium [86
87
88
89
]. The structural changes associated
with the disease are caused, in part, by contribution from increased NO
production [90
, 91
]. Bioactive IL-17 is
detected in RA and osteoarthritis (OA) [49
,
92
] synovial fluid. It stimulates the production of iNOS
and NO levels and other catabolic enzymes in human chondrocytes,
thereby resulting in decreased chondrocyte proliferation and
proteoglycan synthesis [47
, 93
,
94
]. Additionally, IL-17 together with (concomitantly or
concurrently) IL-1ß and TNF stimulate osteoblasts to secrete
cytokines such as GM-CSF and IL-6, which in turn regulate osteoclast
and chondrocyte-mediated resorption and hence, bone and cartilage
destruction [95
96
97
98
99
100
101
]. IL-17 also directly plays a
destructive role in disease progression by inducing matrix
metalloproteinases [48
, 102
,
103
] (especially MMP-1) in synoviocytes, which in turn
initiate tissue damage by proteolytic degradation of collagens and
proteoglycans.
IL-17 and airway neutrophils
IL-17 can also play a proinflammatory role in the airways by
recruiting and activating neutrophils [18
19
20
,
104
, 105
]. Exacerbations of obstructive
airway diseases, including bronchial asthma and chronic obstructive
pulmonary disease (COPD), have resulted in increased neutrophilic
granulocytes that are not associated with any detectable infection
[106
]. The neutrophil recruitment by IL-17 is mediated
in part by CXC chemokine release [20
] or by induction of
endogenous tachykinins that act on natural killer (NK)-1 receptors to
mediate neutrophil recruitment [18
]. In addition to
neutrophil recruitment, IL-17 can also stimulate neutrophil activity in
the airways, because it stimulates release of neutrophil-activating
cytokines IL-6 and IL-8 from bronchial epithelium and fibroblasts
[4
]. The IL-17-induced release of IL-6 and IL-8 is
potentiated by IL-1ß in bronchial epithelial cells [51
,
107
], which in turn can be regulated by IL-17, because
increased IL-1ß is present in obstructive airway diseases
[108
].
IL-17 in other diseases of chronic inflammation
Overproduction of IL-17 has been associated with several chronic
disease conditions, suggesting a role in these diseases. Several
studies point to the association among IL-17, transplant rejection
[14
, 109
110
111
], systemic sclerosis
[112
], psoriasis [27
, 28
,
113
], and promotion of tumor growth
[114
115
116
].
Blocking the effects of IL-17 using IL-17R:Fc inhibits proliferative
responses of T cells to allo-antigens and also significantly prolongs
major histocompatibility complex (MHC)-mismatched, nonvascularized and
vascularized cardiac allograft survival in animal models
[109
, 110
]. Systemic multiple sclerosis
(SSc) is a connective tissue disease of unknown etiology characterized
by fibrosis of the skin, lung, and gastrointestinal tract and by
microvascular abnormalities of the skin and visceral organs
[117
]. Increased IL-17 expression is seen in
CD4+ T cells in the lymphocytes from peripheral blood and
fibrotic lesions of the skin and the lung of affected patients
[112
]. Similarly, a presence of IL-17 is seen in
CD4+ and CD8+ T-cell clones derived from
biopsies from lesional psoriatic skin but not in nonlesional control
biopsies [27
, 113
]. Last but not least,
expression of IL-17 is seen in >50% of ovarian [114
],
endometrial [114
], and cervical cancers
[115
]. Furthermore, in selected cervical cancer cell
lines, IL-17 exhibited angiogenic effects, as tumors from
IL-17-transducted cell lines resulted in increased tumor size
[115
], possibly because of IL-17-mediated, increased
expression of IL-6 and macrophage recruitment.
|
CONCLUSION
|
|---|
The IL-17 family is unique among the known cytokine families in
that all of the members of this family were first identified by
sequence similarity. IL-17 itself was identified as a potentially
interesting molecule based on similarity to the viral open reading
frame HSVS13, and other recently identified family members have been
expanded upon this recognized similarity. Thus, our knowledge of the
IL-17 family, at present, is largely of proteins in search of
biological function. Nonetheless, what has been learned to date of the
functions of IL-17 and the new family members suggests that these
molecules are capable of eliciting profound biological responses and
are therefore likely to play important roles in the fine-tuning of our
immune response. The association of several members of this family with
inflammation and the induction of other cytokines that impact the
inflammatory response suggest that there may be therapeutic use in the
blocking or regulation of the function of these proteins.
|
ACKNOWLEDGEMENTS
|
|---|
We thank Melissa Starovasnik and Gohua Pan for helpful discussions
during the preparation of this manuscript.
Received September 28, 2001;
accepted October 1, 2001.
|
REFERENCES
|
|---|
-
Rouvier, E., Luciani, M. F., Mattei, M. G., Denizot, F., Golstein, P. (1993) CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene J. Immunol. 150,5445-5456[Abstract]
-
Yao, Z., Fanslow, W. C., Seldin, M. F., Rousseau, A. M., Painter, S. L., Comeau, M. R., Cohen, J. I., Spriggs, M. K. (1995) Herpesvirus saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor Immunity 3,811-821[Medline]
-
Kennedy, J., Rossi, D. L., Zurawski, S. M., Vega, F., Jr, Kastelein, R. A., Wagner, J. L., Hannum, C. H., Zlotnik, A. (1996) Mouse IL-17: a cytokine preferentially expressed by alpha beta TCR+CD4-CD8- T cells J. Interferon Cytokine Res. 16,611-617[Medline]
-
Fossiez, F., Djossou, O., Chomarat, P., Flores-Romo, L., Ait-Yahia, S., Maat, C., Pin, J. J., Garrone, P., Garcia, E., Saeland, S., Blanchard, D., Gaillard, C., Das Mahapatra, B., Rouvier, E., Golstein, P., Banchereau, J., Lebecque, S. (1996) T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines J. Exp. Med. 183,2593-2603[Abstract/Free Full Text]
-
Li, H., Chen, J., Huang, A., Stinson, J., Heldens, S., Foster, J., Dowd, P., Gurney, A. L., Wood, W. I. (2000) Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family Proc. Natl. Acad. Sci. USA 97,773-778[Abstract/Free Full Text]
-
Lee, J., Ho, W-H., Maruoka, M., Corpuz, R. T., Baldwin, D. T., Foster, J., Goddard, A. D., Yansura, D. G., Vandlen, R. L., Wood, R. I., Gurney, A. L. (2001) IL17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL17Rh1 J. Biol. Chem. 276,1660-1664[Abstract/Free Full Text]
-
Shi, Y., Ullrich, S. J., Zhang, J., Connolly, K., Grzegorzewski, K. J., Barber, M. C., Wang, W., Wathen, K., Hodge, V., Fisher, C. L., Olsen, H., Ruben, S. M., Knyazev, I., Cho, Y. H., Kao, V., Wilkinson, K. A., Carrell, J. A., Ebner, R. (2000) A novel cytokine receptor-ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity J. Biol. Chem. 275,19167-19176[Abstract/Free Full Text]
-
Hymowitz, S. G., Filvaroff, E., Yin, J. P., Lee, J., Cai, L., Risser, P., Maruoka, M., Mao, W., Foster, J., Kelley, R. F., Pan, G., Gurney, A. L., de Vos, A. M., Starovasnik, M. A. (2001) IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding EMBO J. 20,1-10[Medline]
-
Starnes, T., Robertson, M. J., Sledge, G., Kelich, S., Nakshatri, H., Broxmeyer, H. E., Hromas, R. (2001) IL-17F, a novel cytokine selectively expressed in activated T-cells and monocytes, regulates angiogenesis and endothelial cell cytokine production J. Immunol. 167,4137-4140[Abstract/Free Full Text]
-
Fossiez, F., Banchereau, J., Murray, R., Van Kooten, C., Garrone, P., Lebecque, S. (1998) Interleukin-17 Int. Rev. Immunol. 16,541-551[Medline]
-
Spriggs, M. K. (1997) Interleukin-17 and its receptor J. Clin. Immunol. 17,366-369[Medline]
-
Laan, M., Lotvall, J., Chung, K. F., Linden, A. (2001) IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role of mitogen activated protein (MAP) kinases Br. J. Pharmacol. 133,200-206[Medline]
-
Woltman, A. M., de Haij, S., Boonstra, J. G., Gobin, S. J., Daha, M. R., van Kooten, C. (2000) Interleukin-17 and CD40-ligand synergistically enhance cytokine and chemokine production by renal epithelial cells J. Am. Soc. Nephrol. 11,2044-2055[Abstract/Free Full Text]
-
Van Kooten, C., Boonstra, J. G., Paape, M. E., Fossiez, F., Banchereau, J., Lebecque, S., Bruijn, J. A., De Fijter, J. W., van Es, L. A., Daha, M. R. (1998) Interleukin-17 activates human renal epithelial cells in vitro and is expressed during renal allograft rejection J. Am. Soc. Nephrol. 9,1526-1534[Abstract]
-
Witowski, J., Pawlaczyk, K., Breborowicz, A., Scheuren, A., Kuzlan-Pawlaczyk, M., Wisniewska, J., Polubinska, A., Friess, H., Gahl, G. M., Frei, U., Jorres, A. (2000) IL-17 stimulates intraperitoneal neutrophil infiltration through the release of GRO alpha chemokine from mesothelial cells J. Immunol. 165,5814-5821[Abstract/Free Full Text]
-
Jovanovic, D. V., Di Battista, J. A., Martel-Pelletier, J., Reboul, P., He, Y., Jolicoeur, F. C., Pelletier, J. P. (2001) Modulation of TIMP-1 synthesis by antiinflammatory cytokines and prostaglandin E2 in IL-17 stimulated human monocytes/macrophages J. Rheumatol. 28,712-718[Medline]
-
Fridman, W. H., Tartour, E. (1998) Macrophage- and lymphocyte-produced Th1 and Th2 cytokines in the tumour microenvironment Res. Immunol. 149,651-653[Medline]
-
Hoshino, H., Lotvall, J., Skoogh, B. E., Linden, A. (1999) Neutrophil recruitment by interleukin-17 into rat airways in vivo. Role of tachykinins Am. J. Respir. Crit. Care Med. 159,1423-1428[Abstract/Free Full Text]
-
Linden, A., Hoshino, H., Laan, M. (2000) Airway neutrophils and interleukin-17 Eur. Respir. J. 15,973-977[Abstract]
-
Laan, M., Cui, Z. H., Hoshino, H., Lotvall, J., Sjostand, M., Gruenert, D. C., Skoogh, B. E., Linden, A. (1999) Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways J. Immunol. 162,2347-2352[Abstract/Free Full Text]
-
Cai, X. Y., Gommoll, C. P., Jr, Justice, L., Narula, S. K., Fine, J. S. (1998) Regulation of granulocyte colony-stimulating factor gene expression by interleukin-17 Immunol. Lett. 62,51-58[Medline]
-
Atkins, G. J., Haynes, D. R., Geary, S. M., Loric, M., Crotti, T. N., Findlay, D. M. (2000) Coordinated cytokine expression by stromal and hematopoietic cells during human osteoclast formation Bone 26,653-661[Medline]
-
Schwarzenberger, P., Huang, W., Ye, P., Oliver, P., Manuel, M., Zhang, Z., Bagby, G., Nelson, S., Kolls, J. K. (2000) Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis J. Immunol. 164,4783-4789[Abstract/Free Full Text]
-
Yamamura, Y., Gupta, R., Morita, Y., He, X., Pai, R., Endres, J., Freiberg, A., Chung, K., Fox, D. A. (2001) Effector function of resting T cells: activation of synovial fibroblasts J. Immunol. 166,2270-2275[Abstract/Free Full Text]
-
Yao, Z., Painter, S. L., Fanslow, W. C., Ulrich, D., Macduff, B. M., Spriggs, M. K., Armitage, R. J. (1995) Human IL-17: a novel cytokine derived from T cells J. Immunol. 155,5483-5486[Abstract]
-
Albanesi, C., Cavani, A., Girolomoni, G. (1999) IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-gamma and TNF-alpha J. Immunol. 162,494-502[Abstract/Free Full Text]
-
Teunissen, M. B., Koomen, C. W., de Waal Malefyt, R., Wierenga, E. A., Bos, J. D. (1998) Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes J. Investig. Dermatol. 111,645-649[Medline]
-
Albanesi, C., Scarponi, C., Cavani, A., Federici, M., Nasorri, F., Girolomoni, G. (2000) Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-gamma- and interleukin-4-induced activation of human keratinocytes J. Investig. Dermatol. 115,81-87[Medline]
-
Aarvak, T., Chabaud, M., Miossec, P., Natvig, J. B. (1999) IL-17 is produced by some proinflammatory Th1/Th0 cells but not by Th2 cells J. Immunol. 162,1246-1251[Abstract/Free Full Text]
-
Aarvak, T., Chabaud, M., Kallberg, E., Miossec, P., Natvig, J. B. (1999) Change in the Th1/Th2 phenotype of memory T-cell clones from rheumatoid arthritis synovium Scand. J. Immunol. 50,1-9[Medline]
-
Infante-Duarte, C., Horton, H. F., Byrne, M. C., Kamradt, T. (2000) Microbial lipopeptides induce the production of IL-17 in Th cells J. Immunol. 165,6107-6115[Abstract/Free Full Text]
-
Hsieh, C. S., Macatonia, S. E., Tripp, C. S., Wolf, S. F., O’Garra, A., Murphy, K. M. (1993) Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages Science 260,547-549[Abstract/Free Full Text]
-
Trinchieri, G. (1998) Proinflammatory and immunoregulatory functions of interleukin-12 Int. Rev. Immunol. 16,365-396[Medline]
-
Mosmann, T. R., Cherwinski, M., Bond, M., Gledlin, M. A., Coffman, R. L. (1986) Two types of mouse helper T cell clone. I. Definition according to profile of lymphokine activation and secreted proteins J. Immunol. 136,2348-2357[Abstract]
-
Manetti, R., Parronchi, P., Giudizi, M. G., Piccinni, M-P., Maggi, E., Trinchieri, G., Romagnani, S. (1993) Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type I (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells J. Exp. Med. 177,1199-1204[Abstract/Free Full Text]
-
Moser, M., Murphy, K. M. (2000) Dendritic cell regulation of TH1-TH2 development Nat. Immunol. 1,199-205[Medline]
-
Luzza, F., Parrello, T., Monteleone, G., Sebkova, L., Romano, M., Zarrilli, R., Imeneo, M., Pallone, F. (2000) Up-regulation of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa J. Immunol. 165,5332-5337[Abstract/Free Full Text]
-
Katz, Y., Nadiv, O. (2000) Interleukin-17 may have a central role in inflammatory joint diseases as a "fine-tuning" cytokine Isr. Med. Assoc. J. 2,21-22
-
Thiele, K., Riemann, D., Navarrete Santos, A., Langner, J., Kehlen, A. (2000) Cell-cell contact of human T cells with fibroblasts changes lymphocytic mRNA expression: increased mRNA expression of interleukin-17 and interleukin-17 receptor Eur. Cytokine Netw. 11,53-58[Medline]
-
Cao, Z., Tanaka, M., Regnier, C., Rothe, M., Yamit-hezi, A., Woronicz, J. D., Fuentes, M. E., Durnin, M. H., Dalrymple, S. A., Goeddel, D. V. (1999) NF-kappa B activation by tumor necrosis factor and interleukin-1 Cold Spring Harbor Symp. Quant. Biol. 64,473-483[Medline]
-
Schuster, J. M., Nelson, P. S. (2000) Toll receptors: an expanding role in our understanding of human disease J. Leukoc. Biol. 67,767-773[Abstract]
-
Means, T. K., Golenbock, D. T., Fenton, M. J. (2000) Structure and function of Toll-like receptor proteins Life Sci 68,241-258[Medline]
-
Pan, G., Mao, W., Maruoka, M., French, D., Risser, P., Lee, J., Foster, J., Aggarwal, S., Nicholes, K., Guillet, S., Schow, P., Gurney, A. L. (2001) Overexpression of murine IL-17E induces a Th 2-like response and multi-organ inflammation in transgenic mice J. Immunol. 167,6559-6567[Abstract/Free Full Text]
-
LeGros, G., Ben-Sasson, S. Z., Seder, R., Finkelman, F. D., Paul, W. E. (1990) Generation of interleukin-4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4 producing cells J. Exp. Med. 172,921-929[Abstract/Free Full Text]
-
Ouyang, W., Lohning, M., Gao, Z., Assenmacher, M., Ranganath, S., Radbruch, A., Murphy, K. M. (2000) Stat6-independent GATA-3 autoactivation directs IL-4 independent Th2 development and commitment Immunity 12,27-37[Medline]
-
Chabaud, M., Miossec, P. (2001) The combination of tumor necrosis factor alpha blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflammation and bone resorption in an ex vivo model Arthritis Rheum 44,1293-1303[Medline]
-
Chabaud, M., Lubberts, E., Joosten, L., van Den Berg, W., Miossec, P. (2001) IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis Arthritis Res 3,168-177[Medline]
-
Chabaud, M., Garnero, P., Dayer, J. M., Guerne, P. A., Fossiez, F., Miossec, P. (2000) Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis Cytokine 12,1092-1099[Medline]
-
Chabaud, M., Durand, J. M., Buchs, N., Fossiez, F., Page, G., Frappart, L., Miossec, P. (1999) Human interleukin-17: a T cell-derived proinflammatory cytokine produced by the rheumatoid synovium Arthritis Rheum 42,963-970[Medline]
-
Kotake, S., Udagawa, N., Takahashi, N., Matsuzaki, K., Itoh, K., Ishiyama, S., Saito, S., Inoue, K., Kamatani, N., Gillespie, M. T., Martin, T. J., Suda, T. (1999) IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis J. Clin. Investig. 103,1345-1352[Medline]
-
Jovanovic, D. V., Di Battista, J. A., Martel-Pelletier, J., Jolicoeur, F. C., He, Y., Zhang, M., Mineau, F., Pelletier, J. P. (1998) IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages J. Immunol. 160,3513-3521[Abstract/Free Full Text]
-
Awane, M., Andres, P. G., Li, D. J., Reinecker, H. C. (1999) NF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and ILbeta-induced chemokine promoter activation in intestinal epithelial cells J. Immunol. 162,5337-5344[Abstract/Free Full Text]
-
Epstein, F. H. (1997) Nuclear factor-B: a pivotal transcription factor in chronic inflammatory diseases N. Engl. J. Med. 336,1066-1071[Free Full Text]
-
McDonald, N. Q., Hendrickson, W. A. (1993) A structural superfamily of growth factors containing a cysteine knot motif Cell 73,421-424[Medline]
-
Hearn, M. T., Gomme, P. T. (2000) Molecular architecture and biorecognition processes of the cysteine knot protein superfamily: part I. The glycoprotein hormones J. Mol. Recognit. 13,223-278[Medline]
-
McDonald, N. Q., Lapatto, R., Murray-Rust, J., Gunning, J., Wlodawer, A., Blundell, T. L. (1991) New protein fold revealed by a 2.3-;anA resolution crystal structure of nerve growth factor Nature 354,411-414[Medline]
-
Yano, H., Chao, M. V. (2000) Neurotrophin receptor structure and interactions Pharm. Acta Helv. 74,253-260[Medline]
-
Wiesmann, C., Ultsch, M. H., Bass, S. H., de Vos, A. M. (1999) Crystal structure of nerrve growth factor in complex with the ligand-binding domain of TrkA receptor Nature 401,184-188[Medline]
-
Banner, D. W., D’Arcy, A., Janes, W., Gentz, R., Schoenfeld, H. J., Broger, C., Loetscher, H., Lesslauer, W. (1993) Crystal structure of soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation Cell 73,431-445[Medline]
-
Hymowitz, S. G., Christinger, H. W., Fuh, G., Ultsch, M., O’Connell, M., Kelley, R. F., Ashkenazi, A., de Vos, A. M. (1999) Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5 Mol. Cell 4,563-571[Medline]
-
Mongkolsapaya, J., Grimes, J. M., Chen, N., Xu, X. N., Stuart, D. I., Jones, E. Y., Screaton, G. R. (1999) Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation Nat. Struct. Biol. 6,1048-1053[Medline]
-
Morisato, D., Anderson, K. V. (1994) The spatzle gene encodes a component of the extracellular signaling pathway establishing the dorsal-ventral pattern of the Drosophila embryo Cell 76,677-688[Medline]
-
Morgan, M. M., Mahowald, A. P. (1996) Multiple signaling pathways establish both the individuation and the polarity of the oocyte follicle in Drosophila Arch. Insect Biochem. Physiol. 33,211-230[Medline]
-
Mizuguchi, K., Parker, J. S., Blundell, T. L., Gay, N. L. (1998) Getting knotted: a model for the structure and activation of Spätzle TIBS 23,239-242
-
Morisato, D., Anderson, K. V. (1995) Signaling pathways that establish the dorsal-ventral pattern of the Drosophila embryo Annu. Rev. Genet. 29,371-399[Medline]
-
Roth, S. (1994) Axis determination. Proteolytic generation of a morphogen Curr. Biol. 4,755-757[Medline]
-
Imler, J. L., Hoffmann, J. A. (2000) Toll and Toll-like proteins: an ancient family of receptors signaling infection Rev. Immunogenet. 2,294-304[Medline]
-
Means, T. K., Golenbock, D. T., Fenton, M. J. (2000) Structure and function of Toll-like receptor proteins Life Sci 68,241-258
-
Daun, J. M., Fenton, M. J. (2000) Interleukin-1/Toll receptor family members: receptor structure and signal transduction pathways J. Interferon Cytokine Res. 20,843-855[Medline]
-
Schuster, J. M., Nelson, P. S. (2000) Toll receptors: an expanding role in our understanding of human disease J. Leukoc. Biol. 67,767-773
-
Yao, Z., Timour, M., Painter, S., Fanslow, W., Spriggs, M. (1996) Complete nucleotide sequence of the mouse CTLA8 gene Gene 168,223-225[Medline]
-
Yao, Z., Spriggs, M. K., Derry, J. M., Strockbine, L., Park, L. S., VandenBos, T., Zappone, J. D., Painter, S. L., Armitage, R. J. (1997) Molecular characterization of the human interleukin (IL)-17 receptor Cytokine 9,794-800[Medline]
-
Tian, E., Sawyer, J. R., Largaespada, D. A., Jenkins, N. A., Copeland, N. G., Shaughnessy, J. D., Jr (2000) Evi27 encodes a novel membrane protein with homology to the IL17 receptor Oncogene 19,2098-2109[Medline]
-
Attur, M. G., Patel, R. N., Abramson, S. B., Amin, A. R. (1997) Interleukin-17 up-regulation of nitric oxide production in human osteoarthritis cartilage Arthritis Rheum 40,1050-1053[Medline]
-
Shalom-Barak, T., Quach, J., Lotz, M. (1998) Interleukin-17-induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF-kappaB J. Biol. Chem. 273,27467-27473[Abstract/Free Full Text]
-
Dudler, J., Renggli-Zulliger, N., Busso, N., Lotz, M., So, A. (2000) Effect of interleukin 17 on proteoglycan degradation in murine knee joints Ann. Rheum. Dis. 59,529-532[Abstract/Free Full Text]
-
Lotz, M., Bober, L., Narula, S., Dudler, J. (1996) IL-17 promotes cartilage degradation Arthritis Rheum 39,S120
-
Martel-Pelletier, J., Mineau, F., Jovanovic, D., Di Battista, J. A., Pelletier, J. P. (1999) Mitogen-activated protein kinase and nuclear factor kappa B together regulate interleukin-17-induced nitric oxide production in human osteoarthritic chondrocytes: possible role of transactivating factor mitogen-activated protein kinase-activated protein kinase (MAPKAPK) Arthritis Rheum 42,2399-2409[Medline]
-
Chang, L., Karin, M. (2001) Mammalian MAP kinase signalling cascades Nature 410,37-40[Medline]
-
English, J., Pearson, G., Wilsbacher, J., Swantek, J., Karandikar, M., Xu, S., Cobb, M. H. (1999) New insights into the control of MAP kinase pathways Exp. Cell Res. 253,255-270[Medline]
-
Schwandner, R., Yamaguchi, K., Cao, Z. (2000) Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction J. Exp. Med. 101,1233-1239
-
Broxmeyer, H. E. (1996) Is interleukin 17, an inducible cytokine that stimulates production of other cytokines, merely a redundant player in a sea of other biomolecules? J. Exp. Med. 183,2411-2415[Free Full Text]
-
Schwarzenberger, P., Russa, V. L., Miller, A., Ye, P., Huang, W., Zieske, A., Nelson, S., Bagby, G. J., Stoltz, D., Mynatt, R. L., Spriggs, M., Kolls, J. K. (1998) IL-17 stimulates granulopoiesis in mice: use of an alternate, novel gene therapy-derived method for in vivo evaluation of cytokines J. Immunol. 161,6383-6389[Abstract/Free Full Text]
-
Subramaniam, S. V., Cooper, R. S., Adunyah, S. E. (1999) Evidence for the involvement of JAK/STAT pathway in the signaling mechanism of interleukin-17 Biochem. Biophys. Res. Commun. 262,14-19[Medline]
-
Arend, W. P. (1997) The pathophysiology and treatment of rheumatoid arthritis Arthritis Rheum 40,595-597[Medline]
-
Chizzolini, C., Chicheportiche, R., Burger, D., Dayer, J. M. (1997) Human Th1 cells preferentially induce interleukin (IL)-1 beta while Th2 cells induce IL-1 receptor antagonist production upon cell/cell contact with monocytes Eur. J. Immunol. 27,171-177[Medline]
-
Chomarat, P., Risoan, M. C., Pin, J. J., Banchereau, J., Miossec, P. (1995) Contribution of IL-1, CD14, CD13 in the increased IL-6 production during monocyte synoviocyte interactions J. Immunol. 155,3645-3652[Abstract]
-
Burger, D. (2000) Cell contact interactions in rheumatology Arthritis Res 2,472-476[Medline]
-
Miossec, P. (2000) Are T cells in rheumatoid synovium aggressors or bystanders? Curr. Opin. Rheumatol. 12,181-185[Medline]
-
Van Bezooijen, R. L., Papapoulos, S. E., Lowik, C. W. (2001) Effect of interleukin-17 on nitric oxide production and osteoclastic bone resorption: is there dependency on nuclear factor-kappaB and receptor activator of nuclear factor kappaB (RANK)/RANK ligand signaling? Bone 28,378-386[Medline]
-
Ojo-Amaize, E. A., Kapahi, P., Kakkanaiah, V. N., Takahashi, T., Shalom-Barak, T., Cottam, H. B., Adesomoju, A. A., Nchekwube, E. J., Oyemade, O. A., Karin, M., Okogun, J. I. (2001) Hypoestoxide, a novel anti-inflammatory natural diterpene, inhibits the activity of ikappab kinase Cell. Immunol. 209,149-157[Medline]
-
Kotake, S., Udagawa, N., Takahashi, N., Matsuzaki, K., Itoh, K., Ishiyama, S., Saito, S., Inoue, K., Kamatani, N., Gillespie, M. T., Martin, T. J., Suda, T. (1999) IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis J. Clin. Investig. 103,1345-1352
-
Honorati, M. C., Meliconi, R., Pulsatelli, L., Cane, S., Frizziero, L., Facchini, A. (2001) High in vivo expression of interleukin-17 receptor in synovial endothelial cells and chondrocytes from arthritis patients Rheumatology 40,522-527[Abstract/Free Full Text]
-
Lubberts, E., Joosten, L. A., van de Loo, F. A., van den Gersselaar, L. A., van den Berg, W. B. (2000) Reduction of interleukin-17-induced inhi- bition of chondrocyte proteoglycan synthesis in intact murine articular cartilage by interleukin-4 Arthritis Rheum 43,1300-1306[Medline]
-
Van bezooijen, R. L., Farih-Sips, H. C., Papapoulos, S. E., Lowik, C. W. (1999) Interleukin-17: a new bone acting cytokine in vitro J. Bone Miner. Res. 14,1513-1521[Medline]
-
Chabaud, M., Fossiez, F., Taupin, J. L., Miossec, P. (1998) Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines J. Immunol. 161,409-414[Abstract/Free Full Text]
-
Bush, K. A., Walker, J. S., Lee, C. S., Kirkham, B. W. (2001) Cytokine expression and synovial pathology in the initiation and spontaneous resolution phases of adjuvant arthritis: interleukin-17 expression is upregulated in early disease Clin. Exp. Immunol. 123,487-495[Medline]
-
Lubberts, E., Joosten, L. A., Chabaud, M., van Den Bersselaar, L., Oppers, B., Coenen-De Roo, C. J., Richards, C. D., Miossec, P., van Den Berg, W. B. (2000) IL-4 gene therapy for collagen arthritis suppresses synovial IL-17 and osteoprotegerin ligand and prevents bone erosion J. Clin. Investig. 105,1697-1710[Medline]
-
Chabaud, M., Aarvak, T., Garnero, P., Natvig, J. B., Miossec, P. (2001) Potential contribution of IL-17-producing Th(1)cells to defective repair activity in joint inflammation: partial correction with Th(2)-promoting conditions Cytokine 13,113-118[Medline]
-
Rifas, L., Avioli, L. V. (1999) A novel T cell cytokine stimulates interleukin-6 in human osteoblastic cells J. Bone Miner. Res. 14,1096-1103[Medline]
-
Lenarczyk, A., Helsloot, J., Farmer, K., Peters, L., Sturgess, A., Kirkham, B. (2000) Antigen-induced IL-17 response in the peripheral blood mononuclear cells (PBMC) of healthy controls Clin. Exp. Immunol. 122,41-48[Medline]
-
Jovanovic, D. V., Martel-Pelletier, J., Di Battista, J. A., Mineau, F., Jolicoeur, F. C., Benderdour, M., Pelletier, J. P. () Stimulation of 92-kd gelatinase (matrix metalloproteinase 9) production by interleukin-17 in human monocyte/macrophages: a possible role in rheumatoid arthritis Arthritis Rheum 43,1134-1144
-
Fahmi, H., Di Battista, J. A., Pelletier, J. P., Mineau, F., Ranger, P., Martel-Pelletier, J. (2001) Peroxisome proliferator-activated receptor gamma activators inhibit interleukin-1beta-induced nitric oxide and matrix metalloproteinase 13 production in human chondrocytes Arthritis Rheum 44,595-607[Medline]
-
Larsson, R., Rocksen, D., Lilliehook, B., Jonsson, A., Bucht, A. (2000) Dose-dependent activation of lymphocytes in endotoxin-induced airway inflammation Infect. Immun. 68,6962-6969[Abstract/Free Full Text]
-
Hoshino, H., Laan, M., Sjöstrand, M., Lötvall, J., Skoogh, B. E., Linden, A. (2000) Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo J. Allergy Clin. Immunol. 105,143-149[Medline]
-
Lamblin, C., Gosset, P., Tillie-Leblond, I., Saulnier, F., Marquette, C. H., Wallaert, B., Tonnel, A. B. (1998) Bronchial neutrophilia in patients with noninfectious status asthmaticus Am. J. Respir. Crit. Care Med. 157,394-402[Abstract/Free Full Text]
-
Bedard, M., McLure, C. D., Schiller, N. L., Francoer, C., Cantin, A., Denis, M. (1993) Release of interleukin-8, interleukin-6, and colony stimulating factor by upper airway epithelial cells: implications for cystic fibrosis Am. J. Cell Mol. Biol. 9,455-462
-
Tillie-Leblond, I., Pugin, J., Marquette, C. H., Lamblin, C., Saulnier, F., Brichet, A., Wallaert, B., Tonnel, A. B., Gosset, P. (1999) Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmaticus Am. J. Respir. Crit. Care Med. 159,487-494[Abstract/Free Full Text]
-
Antonysamy, M. A., Fanslowm, W. C., Fu, F., Li, W., Qian, S., Troutt, A. B., Thomson, A. W. (1999) Evidence for a role of IL-17 in alloimmunity: a novel IL-17 antagonist promotes heart graft survival Transplant. Proc. 31,93[Medline]
-
Antonysamy, M. A., Fanslow, W. C., Fu, F., Li, W., Qian, S., Troutt, A. B., Thomson, A. W. (1999) Evidence for a role of IL-17 in organ allograft rejection: IL-17 promotes the functional differentiation of dendritic cell progenitors J. Immunol. 162,577-584[Abstract/Free Full Text]
-
Strehlau, J., Pavlakis, M., Lipman, M., Shapiro, M., Vasconcellos, L., Harmon, W., Strom, T. B. (1997) Quantitative detection of immune activation transcripts as a diagnostic tool in kidney transplantation Proc. Natl. Acad. Sci. USA 94,695-700[Abstract/Free Full Text]
-
Kurasawa, K., Hirose, K., Sano, H., Endo, H., Shinkai, H., Nawata, Y., Takabayashi, K., Iwamoto, I. (2000) Increased interleukin-17 production in patients with systemic sclerosis Arthritis Rheum 43,2455-2563[Medline]
-
Homey, B., Dieu-Nosjean, M. C., Wiesenborn, A., Massacrier, C., Pin, J. J., Oldham, E., Catron, D., Buchanan, M. E., Muller, A., deWaal Malefyt, R., Deng, G., Orozco, R., Ruzicka, T., Lehmann, P., Lebecque, S., Caux, C., Zlotnik, A. (2000) Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis J. Immunol. 164,6621-6632[Abstract/Free Full Text]
-
Kato, T., Furumoto, H., Ogura, T., Onishi, Y., Irahara, M., Yamano, S., Kamada, M., Aono, T. (2001) Expression of IL-17 mRNA in ovarian cancer Biochem. Biophys. Res. Commun. 282,735-738[Medline]
-
Tartour, E., Fossiez, F., Joyeux, I., Galinha, A., Gey, A., Claret, E., Sastre-Garau, X., Couturier, J., Mosseri, V., Vives, V., Banchereau, J., Fridman, W. H., Wijdenes, J., Lebecque, S., Sautes-Fridman, C. (1999) Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice Cancer Res 59,3698-3704[Abstract/Free Full Text]
-
Kehlen, A., Thiele, K., Riemann, D., Rainov, N., Langner, J. (1999) Interleukin-17 stimulates the expression of IkappaB alpha mRNA and the secretion of IL-6 and IL-8 in glioblastoma cell lines J. Neuroimmunol. 101,1-6[Medline]
-
Medsger, T. A. (1993) Systemic sclerosis (scleroderma), localized scleroderma, eosinophilic fasciitis and calcinosis McCarty, D. J. Koopman, W. J. eds. Arthritis and Allied Conditions ,1253-1292 Lea & Febiger Philadelphia.
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ABSTRACT
DISCOVERY OF THE INTERLEUKIN-17...
