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

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...

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Detalles Bibliográficos
Autores principales: Liu, Jianguo, Guan, Xiuqin, Ma, Xiaojing
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118415/
https://www.ncbi.nlm.nih.gov/pubmed/17227910
http://dx.doi.org/10.1084/jem.20061440
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author Liu, Jianguo
Guan, Xiuqin
Ma, Xiaojing
author_facet Liu, Jianguo
Guan, Xiuqin
Ma, Xiaojing
author_sort Liu, Jianguo
collection PubMed
description 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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spelling pubmed-21184152007-12-13 Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathways Liu, Jianguo Guan, Xiuqin Ma, Xiaojing J Exp Med Articles 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. The Rockefeller University Press 2007-01-22 /pmc/articles/PMC2118415/ /pubmed/17227910 http://dx.doi.org/10.1084/jem.20061440 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Liu, Jianguo
Guan, Xiuqin
Ma, Xiaojing
Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathways
title Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathways
title_full Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathways
title_fullStr Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathways
title_full_unstemmed Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathways
title_short Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathways
title_sort regulation of il-27 p28 gene expression in macrophages through myd88- and interferon-γ–mediated pathways
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118415/
https://www.ncbi.nlm.nih.gov/pubmed/17227910
http://dx.doi.org/10.1084/jem.20061440
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AT maxiaojing regulationofil27p28geneexpressioninmacrophagesthroughmyd88andinterferongmediatedpathways