Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0908548 on June 29, 2009

Published online before print June 29, 2009
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Buy
Right arrow All Versions of this Article:
jlb.0908548v1
86/3/655    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Google Scholar
Right arrow Articles by Hreggvidsdottir, H. S.
Right arrow Articles by Harris, H. E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hreggvidsdottir, H. S.
Right arrow Articles by Harris, H. E.
(Journal of Leukocyte Biology. 2009;86:655-662.)
© 2009 Society for Leukocyte Biology

The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation

Hulda Sigridur Hreggvidsdottir*,1, Therese Östberg{dagger},1, Heidi Wähämaa*, Hanna Schierbeck{dagger}, Ann-Charlotte Aveberger{dagger}, Lena Klevenvall{dagger}, Karin Palmblad{dagger}, Lars Ottosson{dagger}, Ulf Andersson{dagger} and Helena Erlandsson Harris*,2

* Department of Medicine, Rheumatology Research Unit, Karolinska Hospital, and
{dagger} Woman and Child Health, Pediatric Unit, Astrid Lindgren Children’s Hospital, Karolinska Institutet, Stockholm, Sweden

2. Correspondence: Department of Medicine, Rheumatology Research Unit, CMM L8:04, Karolinska Hospital, Karolinska Institutet, S-171 76 Stockholm, Sweden. E-mail: helena.erlandsson.harris{at}ki.se

ABSTRACT

The nuclear protein HMGB1 has previously been demonstrated to act as an alarmin and to promote inflammation upon extracellular release, yet its mode of action is still not well defined. Access to highly purified HMGB1 preparations from prokaryotic and eukaryotic sources enabled studies of activation of human PBMC or synovial fibroblast cultures in response to HMGB1 alone or after binding to cofactors. HMGB1 on its own could not induce detectable IL-6 production. However, strong enhancing effects on induction of proinflammatory cytokine production occurred when the protein associated with each of the separate proinflammatory molecules, rhIL-1β, the TLR4 ligand LPS, the TLR9 ligand CpG-ODN, or the TLR1-TLR2 ligand Pam3CSK4. The bioactivities were recorded in cocultures with preformed HMGB1 complexes but not after sequential or simultaneous addition of HMGB1 and the individual ligands. Individual A-box and B-box domains of HMGB1 had the ability to bind LPS and enhance IL-6 production. Heat denaturation of HMGB1 eliminated this enhancement. Cocultures with HMGB1 and other proinflammatory molecules such as TNF, RANKL, or IL-18 did not induce enhancement. HMGB1 thus acts broadly with many but not all immunostimulatory molecules to amplify their activity in a synergistic manner.

Key Words: cell activation • innate cell-mediated immunity




This article has been cited by other articles:


Home page
 J. Immunol.Home page
Y.-H. Qin, S.-M. Dai, G.-S. Tang, J. Zhang, D. Ren, Z.-W. Wang, and Q. Shen
HMGB1 Enhances the Proinflammatory Activity of Lipopolysaccharide by Promoting the Phosphorylation of MAPK p38 through Receptor for Advanced Glycation End Products
J. Immunol., November 15, 2009; 183(10): 6244 - 6250.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
S. Carta, P. Castellani, L. Delfino, S. Tassi, R. Vene, and A. Rubartelli
DAMPs and inflammatory processes: the role of redox in the different outcomes
J. Leukoc. Biol., September 1, 2009; 86(3): 549 - 555.
[Abstract] [Full Text] [PDF]