Published online before print October 2, 2003
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: an overview of signals, mechanisms and functions
,
,1
* Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, Australia;
CRC for Chronic Inflammatory Diseases, Parkville, Victoria, Australia; and
Molecular Genetics Group, Institute of Reproduction and Development, Monash Medical Centre, Monash University, Clayton, Victoria, Australia
1 Correspondence: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia. E-mail: D.Hume{at}imb.uq.edu.au
Interferon-
(IFN-) coordinates a diverse array of cellular programs through transcriptional regulation of immunologically relevant genes. This article reviews the current understanding of IFN- ligand, receptor, signal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophage function during infection. The current model for IFN- signal transduction is discussed, as well as signal regulation and factors conferring signal specificity. Cellular effects of IFN- are described, including up-regulation of pathogen recognition, antigen processing and presentation, the antiviral state, inhibition of cellular proliferation and effects on apoptosis, activation of microbicidal effector functions, immunomodulation, and leukocyte trafficking. In addition, integration of signaling and response with other cytokines and pathogen-associated molecular patterns, such as tumor necrosis factor-
, interleukin-4, type I IFNs, and lipopolysaccharide are discussed.
Key Words: macrophage • cytokine • lipopolysaccharide • Toll-like receptor • inflammation
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I. K. Mullarky, F. M. Szaba, L. W. Kummer, L. B. Wilhelm, M. A. Parent, L. L. Johnson, and S. T. Smiley Gamma Interferon Suppresses Erythropoiesis via Interleukin-15 Infect. Immun., May 1, 2007; 75(5): 2630 - 2633. [Abstract] [Full Text] [PDF]
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L. Li, L. Huang, S.-s. J. Sung, P. I. Lobo, M. G. Brown, R. K. Gregg, V. H. Engelhard, and M. D. Okusa NKT Cell Activation Mediates Neutrophil IFN-{gamma} Production and Renal Ischemia-Reperfusion Injury J. Immunol., May 1, 2007; 178(9): 5899 - 5911. [Abstract] [Full Text] [PDF]
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 K. M.A. Rogers, M. Thomas, L. Galligan, T. R. Wilson, W. L. Allen, H. Sakai, P. G. Johnston, and D. B. Longley Cellular FLICE-inhibitory protein regulates chemotherapy-induced apoptosis in breast cancer cells Mol. Cancer Ther., May 1, 2007; 6(5): 1544 - 1551. [Abstract] [Full Text] [PDF]
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G. Woszczek, L.-Y. Chen, S. Nagineni, S. Alsaaty, A. Harry, C. Logun, R. Pawliczak, and J. H. Shelhamer IFN-{gamma} Induces Cysteinyl Leukotriene Receptor 2 Expression and Enhances the Responsiveness of Human Endothelial Cells to Cysteinyl Leukotrienes J. Immunol., April 15, 2007; 178(8): 5262 - 5270. [Abstract] [Full Text] [PDF]
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 K. Kusaba, H. Kai, M. Koga, N. Takayama, A. Ikeda, H. Yasukawa, Y. Seki, K. Egashira, and T. Imaizumi Inhibition of Intrinsic Interferon-{gamma} Function Prevents Neointima Formation After Balloon Injury Hypertension, April 1, 2007; 49(4): 909 - 915. [Abstract] [Full Text] [PDF]
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V. Hurgin, D. Novick, A. Werman, C. A. Dinarello, and M. Rubinstein Antiviral and immunoregulatory activities of IFN-{gamma} depend on constitutively expressed IL-1{alpha} PNAS, March 20, 2007; 104(12): 5044 - 5049. [Abstract] [Full Text] [PDF]
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M. Zhang, S. Byrne, N. Liu, Y. Wang, A. Oxenius, and P. G. Ashton-Rickardt Differential Survival of Cytotoxic T Cells and Memory Cell Precursors J. Immunol., March 15, 2007; 178(6): 3483 - 3491. [Abstract] [Full Text] [PDF]
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B. Becknell, T. L. Hughes, A. G. Freud, B. W. Blaser, J. Yu, R. Trotta, H. C. Mao, M. L. Caligiuri de Jesus, M. Alghothani, D. M. Benson Jr, et al. Hlx homeobox transcription factor negatively regulates interferon-{gamma} production in monokine-activated natural killer cells Blood, March 15, 2007; 109(6): 2481 - 2487. [Abstract] [Full Text] [PDF]
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I. J. Glomski, J.-P. Corre, M. Mock, and P. L. Goossens Cutting Edge: IFN-{gamma}-Producing CD4 T Lymphocytes Mediate Spore-Induced Immunity to Capsulated Bacillus anthracis J. Immunol., March 1, 2007; 178(5): 2646 - 2650. [Abstract] [Full Text] [PDF]
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G. Mancuso, A. Midiri, C. Biondo, C. Beninati, S. Zummo, R. Galbo, F. Tomasello, M. Gambuzza, G. Macri, A. Ruggeri, et al. Type I IFN Signaling Is Crucial for Host Resistance against Different Species of Pathogenic Bacteria J. Immunol., March 1, 2007; 178(5): 3126 - 3133. [Abstract] [Full Text] [PDF]
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K. Ramsauer, M. Farlik, G. Zupkovitz, C. Seiser, A. Kroger, H. Hauser, and T. Decker Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-{gamma}-inducible gbp2 gene PNAS, February 20, 2007; 104(8): 2849 - 2854. [Abstract] [Full Text] [PDF]
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D. Vremec, M. O'Keeffe, H. Hochrein, M. Fuchsberger, I. Caminschi, M. Lahoud, and K. Shortman Production of interferons by dendritic cells, plasmacytoid cells, natural killer cells, and interferon-producing killer dendritic cells Blood, February 1, 2007; 109(3): 1165 - 1173. [Abstract] [Full Text] [PDF]
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J. Liu, X. Guan, and X. Ma Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-{gamma}-mediated pathways J. Exp. Med., January 22, 2007; 204(1): 141 - 152. [Abstract] [Full Text] [PDF]
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J. R. Abend, J. A. Low, and M. J. Imperiale Inhibitory Effect of Gamma Interferon on BK Virus Gene Expression and Replication J. Virol., January 1, 2007; 81(1): 272 - 279. [Abstract] [Full Text] [PDF]
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N. L. Korpi-Steiner, M. E. Bates, W.-M. Lee, D. J. Hall, and P. J. Bertics Human rhinovirus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation J. Leukoc. Biol., December 1, 2006; 80(6): 1364 - 1374. [Abstract] [Full Text] [PDF]
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U. I. Chaudhry, T. P. Kingham, G. Plitas, S. C. Katz, J. R. Raab, and R. P. DeMatteo Combined Stimulation with Interleukin-18 and CpG Induces Murine Natural Killer Dendritic Cells to Produce IFN-{gamma} and Inhibit Tumor Growth Cancer Res., November 1, 2006; 66(21): 10497 - 10504. [Abstract] [Full Text] [PDF]
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N. Vazquez, T. Greenwell-Wild, S. Rekka, J. M. Orenstein, and S. M. Wahl Mycobacterium avium-induced SOCS contributes to resistance to IFN-{gamma}-mediated mycobactericidal activity in human macrophages J. Leukoc. Biol., November 1, 2006; 80(5): 1136 - 1144. [Abstract] [Full Text] [PDF]
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H. Negishi, Y. Fujita, H. Yanai, S. Sakaguchi, X. Ouyang, M. Shinohara, H. Takayanagi, Y. Ohba, T. Taniguchi, and K. Honda Evidence for licensing of IFN-{gamma}-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program PNAS, October 10, 2006; 103(41): 15136 - 15141. [Abstract] [Full Text] [PDF]
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M. A. Samuel and M. S. Diamond Pathogenesis of West Nile Virus Infection: a Balance between Virulence, Innate and Adaptive Immunity, and Viral Evasion J. Virol., October 1, 2006; 80(19): 9349 - 9360. [Full Text] [PDF]
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X. Zhu, M. S. Chang, R. C. Hsueh, R. Taussig, K. D. Smith, M. I. Simon, and S. Choi Dual Ligand Stimulation of RAW 264.7 Cells Uncovers Feedback Mechanisms That Regulate TLR-Mediated Gene Expression J. Immunol., October 1, 2006; 177(7): 4299 - 4310. [Abstract] [Full Text] [PDF]
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 S. M. Mense, A. Sengupta, C. Lan, M. Zhou, G. Bentsman, D. J. Volsky, R. M. Whyatt, F. P. Perera, and L. Zhang The Common Insecticides Cyfluthrin and Chlorpyrifos Alter the Expression of a Subset of Genes with Diverse Functions in Primary Human Astrocytes Toxicol. Sci., September 1, 2006; 93(1): 125 - 135. [Abstract] [Full Text] [PDF]
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P. K. Henke, C. G. Pearce, D. M. Moaveni, A. J. Moore, E. M. Lynch, C. Longo, M. Varma, N. A. Dewyer, K. B. Deatrick, G. R. Upchurch Jr, et al. Targeted Deletion of CCR2 Impairs Deep Vein Thombosis Resolution in a Mouse Model. J. Immunol., September 1, 2006; 177(5): 3388 - 3397. [Abstract] [Full Text] [PDF]
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 H. T. Aung, K. Schroder, S. R. Himes, K. Brion, W. van Zuylen, A. Trieu, H. Suzuki, Y. Hayashizaki, D. A. Hume, M. J. Sweet, et al. LPS regulates proinflammatory gene expression in macrophages by altering histone deacetylase expression FASEB J, July 1, 2006; 20(9): 1315 - 1327. [Abstract] [Full Text] [PDF]
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 R. Zhou, W. Tang, Y.-X. Ren, P.-L. He, F. Zhang, L.-P. Shi, Y.-F. Fu, Y.-C. Li, S. Ono, H. Fujiwara, et al. (5R)-5-Hydroxytriptolide Attenuated Collagen-Induced Arthritis in DBA/1 Mice via Suppressing Interferon-{gamma} Production and Its Related Signaling J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 35 - 44. [Abstract] [Full Text] [PDF]
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