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Cutting Edge: Involvement of the Type I IFN Production and Signaling Pathway in Lipopolysaccharide-Induced IL-10 Production¹

Elmer Y. Chang^2,*,,, Beichu Guo^2,*, Sean E. Doyle^* and Genhong Cheng^3,*,

^* Department of Microbiology, Immunology, and Molecular Genetics, Division of Digestive Diseases, Specialty Training and Advanced Research Program, and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095

Macrophages respond to LPS by the rapid activation of proinflammatory cytokines that serve to initiate host defense against microbial invasion. To prevent injury to the host from excess production of these cytokines, IL-10 is up-regulated to feedback inhibit the proinflammatory response. However, the molecular events responsible for LPS-induced up-regulation of IL-10 remain to be elucidated. In this study, we provide evidence that production of and signaling by type I IFN is required for LPS-induced IL-10 up-regulation. In addition, we demonstrate that defect in type I IFN production and signaling results in a trend toward LPS-mediated superinduction of proinflammatory genes and cytokines in bone marrow-derived macrophages. Our findings suggest a novel anti-inflammatory role for the type I IFN production and signaling pathway in regulating LPS response in bone marrow-derived macrophages.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health Research Grants R01 AI056154, R01 AI069120, and R37 AI47868. E.Y.C. is supported by a research fellowship from the Crohn’s and Colitis Foundation of America. B.G. is supported by a Special Fellowship from the Lymphoma and Leukemia Society.

² E.Y.C. and B.G. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Genhong Cheng, Department of Microbiology, Immunology, and Molecular Genetics, 8-240 Factor Building, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095. E-mail address: gcheng{at}mednet.ucla.edu

⁴ Abbreviations used in this paper: TRIF, Toll/IL-1R homology domain-containing adaptor-inducing IFN-; BMDM, bone marrow-derived macrophage; CHX, cycloheximide; CM, conditioned medium; IRF3, IFN regulatory factor 3; Q-PCR, quantitative PCR; WT, wild type.

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