Journal of Gastroenterology

, 44:1172

Interleukin 10 inhibits interferon γ- and tumor necrosis factor α-stimulated activation of NADPH oxidase 1 in human colonic epithelial cells and the mouse colon

  • Mai Kamizato
  • Kensei Nishida
  • Kiyoshi Masuda
  • Keiko Takeo
  • Yuta Yamamoto
  • Tomoko Kawai
  • Shigetada Teshima-Kondo
  • Toshihito Tanahashi
  • Kazuhito Rokutan
Original Article—Alimentary Tract

Abstract

Background

NADPH oxidase 1 (Nox1) is preferentially expressed in the colon, but its functional role is not fully understood. This study was designed to elucidate a potential role of Nox1 in inflammation of the colon.

Methods

Superoxide production by T84 cells was measured by the cytochrome c method. Protein and mRNA levels of Nox1 and Nox organizer 1 (NOXO1) in the cells were measured by real-time reverse transcriptase PCR and Western blotting, respectively. Expression of Nox1, Nox2, dual oxidase 2 (Duox2), NOXO1, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α mRNAs was measured in proximal, middle, and distal portions of colonic mucosas from male wild-type C57BL/6J and interleukin (IL)-10 knockout mice at 6, 10, and 16 weeks of age. Grading of inflammation was done by scoring histological changes.

Results

IL-10 significantly inhibited IFN-γ- or TNF-α-induced up-regulation of superoxide-producing activity in T84 cells by suppressing expression of Nox1 mRNA and protein. IL-10 also inhibited TNF-α-stimulated induction of NOXO1 and p38 MAPK phosphorylation. Levels of Nox1, but not Nox2 or Duox2 mRNA, was age-dependently increased following a gradient with low levels in the proximal colon and high levels in the distal colon of the wild-type mice. The absence of IL-10 significantly facilitated Nox1 expression in association with increased IFN-γ mRNA expression before the development of spontaneous colitis and age-dependently accelerated their mRNA expression.

Conclusions

IL-10 may be a possible down-regulator of the Nox1-based oxidase in the colon, suggesting a potential role of reactive oxygen species (ROS) derived from Nox1-based oxidase in inflammation of the colon.

Keywords

Interleukin 10 Interferon γ Tumor necrosis factor α NADPH oxidase 1 Colon 

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Copyright information

© Springer 2009

Authors and Affiliations

  • Mai Kamizato
    • 1
  • Kensei Nishida
    • 1
  • Kiyoshi Masuda
    • 1
  • Keiko Takeo
    • 1
  • Yuta Yamamoto
    • 1
  • Tomoko Kawai
    • 1
  • Shigetada Teshima-Kondo
    • 1
  • Toshihito Tanahashi
    • 1
  • Kazuhito Rokutan
    • 1
  1. 1.Department of Stress Science, Institute of Health BiosciencesThe University of Tokushima Graduate SchoolTokushimaJapan

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