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* Department of Infectious Diseases and
Hartwell Center for Biotechnology and Bioinformatics, St. Jude Children’s Research Hospital, Memphis, TN 38015
IL-10 regulates inflammation by reducing cytokine and chemokine production from activated macrophages. We performed microarray experiments to identify possible effector molecules of IL-10 and to investigate the global effect of IL-10 on the transcriptional response induced in LPS-activated macrophages. To exclude background effects of endogenous IL-10, macrophages from IL-10-deficient mice were used. IL-10 up-regulated expression of a small number of genes (26 and 37 after 45 min and 3 h, respectively), including newly identified and previously documented targets such as suppressor of cytokine signaling-3 and IL-1 receptor antagonist. However, the activation program triggered by LPS was profoundly affected by IL-10. IL-10 repressed 62 and further increased 15 of 259 LPS-induced genes. For all genes examined, the effects of IL-10 were determined to be STAT3-dependent. These results suggest that IL-10 regulates STAT3-dependent pathways that selectively target a broad component of LPS-induced genes at the mRNA level.
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R. P. Donnelly, F. Sheikh, S. V. Kotenko, and H. Dickensheets The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain J. Leukoc. Biol., August 1, 2004; 76(2): 314 - 321. [Abstract] [Full Text] [PDF]
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A.-L. Pauleau, R. Rutschman, R. Lang, A. Pernis, S. S. Watowich, and P. J. Murray Enhancer-Mediated Control of Macrophage-Specific Arginase I Expression J. Immunol., June 15, 2004; 172(12): 7565 - 7573. [Abstract] [Full Text] [PDF]
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N. E. Rodriguez, H. K. Chang, and M. E. Wilson Novel Program of Macrophage Gene Expression Induced by Phagocytosis of Leishmania chagasi Infect. Immun., April 1, 2004; 72(4): 2111 - 2122. [Abstract] [Full Text] [PDF]
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L. Zhou, A. A. Nazarian, and S. T. Smale Interleukin-10 Inhibits Interleukin-12 p40 Gene Transcription by Targeting a Late Event in the Activation Pathway Mol. Cell. Biol., March 15, 2004; 24(6): 2385 - 2396. [Abstract] [Full Text] [PDF]
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S. Fernandez, P. Jose, M. G. Avdiushko, A. M. Kaplan, and D. A. Cohen Inhibition of IL-10 Receptor Function in Alveolar Macrophages by Toll-Like Receptor Agonists J. Immunol., February 15, 2004; 172(4): 2613 - 2620. [Abstract] [Full Text] [PDF]
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A. C. Morrison, C. B. Wilson, M. Ray, and P. H. Correll Macrophage-Stimulating Protein, the Ligand for the Stem Cell-Derived Tyrosine Kinase/RON Receptor Tyrosine Kinase, Inhibits IL-12 Production by Primary Peritoneal Macrophages Stimulated with IFN-{gamma} and Lipopolysaccharide J. Immunol., February 1, 2004; 172(3): 1825 - 1832. [Abstract] [Full Text] [PDF]
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L. Williams, L. Bradley, A. Smith, and B. Foxwell Signal Transducer and Activator of Transcription 3 Is the Dominant Mediator of the Anti-Inflammatory Effects of IL-10 in Human Macrophages J. Immunol., January 1, 2004; 172(1): 567 - 576. [Abstract] [Full Text] [PDF]
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H. Kuwata, Y. Watanabe, H. Miyoshi, M. Yamamoto, T. Kaisho, K. Takeda, and S. Akira IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-{alpha} production in macrophages Blood, December 1, 2003; 102(12): 4123 - 4129. [Abstract] [Full Text] [PDF]
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