Interleukin (IL)-27 is the newest member of the IL-12 family of heterodimeric cytokines composed of the Epstein-Barr virus–induced gene 3 and p28 chains. IL-27 not only plays an important role in the regulation of differentiation of naive T helper cells but also possesses antiinflammatory properties. IL-27 is an early product of activated monocytes/macrophages and dendritic cells. However, the mechanisms whereby inflammatory signals stimulate IL-27 production have not been explored. In this study, we investigated the transcriptional regulation of the mouse IL-27 p28 gene in macrophages in response to lipopolysaccharide (LPS) and interferon (IFN)-γ. We found that LPS-stimulated p28 production was completely dependent on the Toll-like receptor 4/myeloid differentiation factor 88 (MyD88)–mediated pathway but only partially dependent on nuclear factor κB c-Rel. IFN-γ–induced p28 production/secretion was also partially dependent on MyD88 but independent of c-Rel. We then cloned the mouse p28 gene promoter and mapped its multiple transcription initiation sites. Furthermore, we identified critical promoter elements that mediate the inductive effects of LPS and IFN-γ, separately and synergistically, on p28 gene transcription in a c-Rel– and interferon regulatory factor 1–dependent manner, respectively.
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22 January 2007
Article|
January 16 2007
Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathways
Jianguo Liu,
Jianguo Liu
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021
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Xiuqin Guan,
Xiuqin Guan
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021
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Xiaojing Ma
Xiaojing Ma
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021
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Jianguo Liu
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021
Xiuqin Guan
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021
Xiaojing Ma
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021
CORRESPONDENCE Xiaojing Ma: [email protected]
Abbreviations used: BMDM, bone marrow–derived macrophages; ChIP, chromatin immunoprecipitation; EBI3, Epstein-Barr virus–induced gene 3; EMSA, electrophoretic mobility shift assay; IRF, interferon regulatory factor; mRNA, messenger RNA; MyD88, myeloid differentiation factor 88; qPCR, real-time quantitative PCR; RLM-RACE, 5′ RNA ligase-mediated rapid amplification of cDNA end; TIS, transcription initiation site; TLR, Toll-like receptor.
Received:
July 07 2006
Accepted:
December 06 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (1): 141–152.
Article history
Received:
July 07 2006
Accepted:
December 06 2006
Citation
Jianguo Liu, Xiuqin Guan, Xiaojing Ma; Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathways . J Exp Med 22 January 2007; 204 (1): 141–152. doi: https://doi.org/10.1084/jem.20061440
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