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Downregulation of CPI-17 contributes to dysfunctional motility in chronic intestinal inflammation model mice and ulcerative colitis patients

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Abstract

Background

Chronic intestinal inflammation is frequently accompanied by motility disorders. We previously reported that proinflammatory cytokines, such as tumor necrosis factor α and interleukin (IL)-1β downregulate CPI-17, an endogenous inhibitor of serine/threonine protein phosphatase in smooth-muscle cells, which results in the inhibition of myosin light chain phosphorylation and contractility. However, its clinical relevance has not been clarified.

Methods

The present study examined the changes in CPI-17 expression in chronic intestinal inflammation using smooth-muscle tissues from IL-10 knockout mice and from patients with ulcerative colitis (UC).

Results

The IL-10 knockout mice developed spontaneous and chronic colitis accompanied by immune cell infiltration, submucosal fibrosis, and thickening of the muscularis externa. The expression of α-smooth muscle actin protein in the smooth-muscle layer did not change, whereas that of CPI-17 protein was decreased by about 40% compared with healthy wild-type controls. Consistent with this observation, smooth-muscle contractile force and myosin light chain phosphorylation induced by a muscarinic agonist were reduced in the knockout mice. Moreover, we observed that CPI-17 protein expression was decreased in smooth-muscle tissues from patients with UC compared with controls.

Conclusions

CPI-17 downregulation might contribute to the decreased motor function in chronic inflammatory bowel diseases.

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Authors and Affiliations

  1. Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan

    Takashi Ohama, Masatoshi Hori, Masahiko Fujisawa, Masaharu Kiyosue, Takahisa Murata & Hiroshi Ozaki

  2. Gastroenterology Research, Drug Discovery Department II, Pharmaceutical Research Laboratories, Ajinomoto Pharmaceutical Company, Inc., Kawasaki, Japan

    Masaki Hashimoto & Yuka Ikenoue

  3. Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

    Yoshio Jinno, Hiroto Miwa & Takayuki Matsumoto

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  1. Takashi Ohama
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  2. Masatoshi Hori
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  3. Masahiko Fujisawa
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  4. Masaharu Kiyosue
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Ohama, T., Hori, M., Fujisawa, M. et al. Downregulation of CPI-17 contributes to dysfunctional motility in chronic intestinal inflammation model mice and ulcerative colitis patients. J Gastroenterol 43, 858–865 (2008). https://doi.org/10.1007/s00535-008-2241-2

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  • DOI: https://doi.org/10.1007/s00535-008-2241-2

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