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

Shigeru Oshima, Tetsuya Nakamura, Shin Namiki, Eriko Okada, Kiichiro Tsuchiya, Ryuichi Okamoto, Motomi Yamazaki, Takanori Yokota, Masatoshi Aida, Yuki Yamaguchi, Takanori Kanai, Hiroshi Handa, Mamoru Watanabe

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88 Citations (Scopus)

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-γ) 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-γ-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 results suggest that the functional interplay between IRF-1 and IRF-2 serves as an elaborate and cooperative mechanism for timely as well as continuous regulation of IL-7 production that is essential for local immune regulation within human intestinal mucosa.

Original languageEnglish
Pages (from-to)6298-6310
Number of pages13
JournalMolecular and cellular biology
Volume24
Issue number14
DOIs
Publication statusPublished - 2004 Jul

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Oshima, S., Nakamura, T., Namiki, S., Okada, E., Tsuchiya, K., Okamoto, R., Yamazaki, M., Yokota, T., Aida, M., Yamaguchi, Y., Kanai, T., Handa, H., & Watanabe, M. (2004). 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, 24(14), 6298-6310. https://doi.org/10.1128/MCB.24.14.6298-6310.2004