Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells

Molecular and Cellular Biology
Shigeru OshimaMamoru Watanabe

Abstract

Intestinal epithelial cell-derived interleukin (IL)-7 functions as a pleiotropic and nonredundant cytokine in the human intestinal mucosa; however, the molecular basis of its production has remained totally unknown. We here showed that human intestinal epithelial cells both constitutively and when induced by gamma interferon (IFN-gamma) produced IL-7, while several other factors we tested had no effect. Transcriptional regulation via an IFN regulatory factor element (IRF-E) on the 5' flanking region, which lacks canonical core promoter sequences, was pivotal for both modes of IL-7 expression. IRF-1 and IRF-2, the latter of which is generally known as a transcriptional repressor, were shown to interact with IRF-E and transactivate IL-7 gene expression in an IFN-gamma-inducible and constitutive manner, respectively. Indeed, tetracycline-inducible expression experiments revealed that both of these IRF proteins up-regulated IL-7 protein production, and their exclusive roles were further confirmed by small interfering RNA-mediated gene silencing systems. Moreover, these IRFs displayed distinct properties concerning the profile of IL-7 transcripts upon activation and expression patterns within human colonic epithelial tissues. These ...Continue Reading

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Citations

Sep 22, 2006·Journal of Gastroenterology·Tsuyoshi YamashiroMamoru Watanabe
Jan 11, 2012·Clinical Reviews in Allergy & Immunology·Robert C AxtellLawrence Steinman
Jul 31, 2013·Immunology and Cell Biology·Asami HanazawaToshinori Nakayama
Sep 8, 2010·The Journal of Biological Chemistry·Angeli MöllerKathryn L Ball
Mar 13, 2009·The Journal of Biological Chemistry·Masakiyo SakaguchiNam-ho Huh
Aug 28, 2004·Journal of Virology·Nobuhiko KanazawaMamoru Watanabe
Jun 30, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·John R KluneDavid A Geller
Nov 6, 2010·BMC Molecular Biology·Marieta GenchevaJohn E Shively
Nov 1, 2006·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Mamoru Watanabe
Feb 14, 2009·Journal of Gastroenterology·Minekazu MurayamaMamoru Watanabe
May 1, 2012·Seminars in Immunology·Cedric Vonarbourg, Andreas Diefenbach
Mar 27, 2012·Seminars in Immunology·Hsin-Ying Huang, Sanjiv A Luther
Jul 4, 2015·Journal of Gastroenterology·Ryuichi Okamoto, Mamoru Watanabe
Feb 23, 2010·Biochemical and Biophysical Research Communications·Junko AkiyamaMamoru Watanabe
Jul 29, 2008·Cytokine·Atsushi YoshiokaMamoru Watanabe
Jul 26, 2008·Journal of Cellular Biochemistry·Seema SaksenaPradeep K Dudeja
Aug 7, 2010·European Journal of Immunology·Shabnam ShalapourThomas Schüler
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Mar 7, 2017·Acta Pharmacologica Sinica·Shou-Cai ZhaoFudong Liu
Mar 5, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tor Espen Stav-NoraasJohanna Hol

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