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Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis

  • Original Article—Alimentary Tract
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Abstract

Background

Interleukin (IL)-33 is a cytokine belonging to the IL-1 family. IL-33 has been shown to elicit a Th2-like cytokine response in immune cells. In this study, we investigated IL-33 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for IL-33 expression in human colonic subepithelial myofibroblasts (SEMFs).

Methods

IL-33 mRNA expression was determined by real-time polymerase chain reaction (PCR). IL-33 expression in the IBD mucosa was evaluated by immunohistochemical methods.

Results

IL-33 mRNA expression was significantly elevated in active lesions from patients with ulcerative colitis (UC), but was not detected in inactive lesions from UC patients or in lesions from patients with either active or inactive Crohn’s disease. Colonic SEMFs were identified as a major source of IL-33 in the mucosa. IL-1β and tumor necrosis factor-α (TNF-α) significantly enhanced IL-33 mRNA and protein expression in isolated colonic SEMFs. IL-1β and TNF-α did not affect IL-33 expression in intestinal epithelial cell lines (HT-29 and Caco-2 cells). This IL-1β- and TNF-α-induced IL-33 mRNA expression was mediated by p42/44 mitogen activated protein kinase (MAPK) pathway-dependent activation of nuclear factor (NF)-κB and activator protein (AP)-1.

Conclusions

IL-33, derived from colonic SEMFs, may play an important role in the pathophysiology of UC.

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Authors and Affiliations

  1. Department of Medicine, Shiga University of Medical Science, Seta Tukinowa, Otsu, 520-2192, Japan

    Ayako Kobori, Yuhki Yagi, Hirotsugu Imaeda, Hiromitsu Ban, Shigeki Bamba, Tomoyuki Tsujikawa, Yasuharu Saito & Yoshihide Fujiyama

  2. Division of Mucosal Immunology, Graduate School of Medicine, Shiga University of Medical Science, Seta Tukinowa, Otsu, 520-2192, Japan

    Akira Andoh

Authors
  1. Ayako Kobori
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  2. Yuhki Yagi
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  3. Hirotsugu Imaeda
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  4. Hiromitsu Ban
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  5. Shigeki Bamba
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  6. Tomoyuki Tsujikawa
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  7. Yasuharu Saito
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  8. Yoshihide Fujiyama
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  9. Akira Andoh
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Corresponding author

Correspondence to Akira Andoh.

Additional information

A. Kobori and Y. Yagi contributed equally to this work.

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Kobori, A., Yagi, Y., Imaeda, H. et al. Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol 45, 999–1007 (2010). https://doi.org/10.1007/s00535-010-0245-1

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  • DOI: https://doi.org/10.1007/s00535-010-0245-1

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