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

Research output: Contribution to journalArticle

82 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
Externally publishedYes

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Interferon Regulatory Factor-1
Interleukin-7
Up-Regulation
Epithelial Cells
Gene Expression
Intestinal Mucosa
5' Flanking Region
Gene Silencing
Tetracycline
Interferons
Small Interfering RNA
Interferon-gamma
Proteins
Epithelium
Cytokines

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells. / Oshima, Shigeru; Nakamura, Tetsuya; Namiki, Shin; Okada, Eriko; Tsuchiya, Kiichiro; Okamoto, Ryuichi; Yamazaki, Motomi; Yokota, Takanori; Aida, Masatoshi; Yamaguchi, Yuki; Kanai, Takanori; Handa, Hiroshi; Watanabe, Mamoru.

In: Molecular and Cellular Biology, Vol. 24, No. 14, 07.2004, p. 6298-6310.

Research output: Contribution to journalArticle

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, vol. 24, no. 14, pp. 6298-6310. https://doi.org/10.1128/MCB.24.14.6298-6310.2004
Oshima, Shigeru ; Nakamura, Tetsuya ; Namiki, Shin ; Okada, Eriko ; Tsuchiya, Kiichiro ; Okamoto, Ryuichi ; Yamazaki, Motomi ; Yokota, Takanori ; Aida, Masatoshi ; Yamaguchi, Yuki ; Kanai, Takanori ; Handa, Hiroshi ; Watanabe, Mamoru. / Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 14. pp. 6298-6310.
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AU - Nakamura, Tetsuya

AU - Namiki, Shin

AU - Okada, Eriko

AU - Tsuchiya, Kiichiro

AU - Okamoto, Ryuichi

AU - Yamazaki, Motomi

AU - Yokota, Takanori

AU - Aida, Masatoshi

AU - Yamaguchi, Yuki

AU - Kanai, Takanori

AU - Handa, Hiroshi

AU - Watanabe, Mamoru

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