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Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-gamma-mediated pathways.

TitleRegulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-gamma-mediated pathways.
Publication TypeJournal Article
Year of Publication2007
AuthorsLiu J, Guan X, Ma X
JournalJ Exp Med
Volume204
Issue1
Pagination141-52
Date Published2007 Jan 22
ISSN0022-1007
KeywordsAnimals, Base Sequence, Binding Sites, DNA, Complementary, Female, Gene Expression Regulation, In Vitro Techniques, Interferon Regulatory Factor-1, Interferon-gamma, Interleukins, Lipopolysaccharides, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular Sequence Data, Myeloid Differentiation Factor 88, NF-kappa B, Promoter Regions, Genetic, Protein Subunits, Recombinant Proteins, RNA, Messenger, Signal Transduction, Transcription, Genetic
Abstract

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)-gamma. 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 kappaB c-Rel. IFN-gamma-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-gamma, separately and synergistically, on p28 gene transcription in a c-Rel- and interferon regulatory factor 1-dependent manner, respectively.

DOI10.1084/jem.20061440
Alternate JournalJ Exp Med
PubMed ID17227910
PubMed Central IDPMC2118415
Grant ListR01 CA100223 / CA / NCI NIH HHS / United States
CA100223 / CA / NCI NIH HHS / United States

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