IL-17A Induces Hypo-contraction of Intestinal Smooth Muscle via Induction of iNOS in Muscularis Macrophages

Journal of Pharmacological Sciences

Hiroshi Ozaki¹  Masatoshi Hori¹  Osamu Kaminuma²  Takachika Hiroi²  Nobumasa Watanabe²  Takahisa Murata¹  Daisuke Mori¹ 

[1] Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan;Department of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science, Japan

关键词: IL-17A;    macrophage;    iNOS;    intestinal inflammation;    smooth muscle;   

DOI  :  10.1254/jphs.14060FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(43)Cited-By(3)Intestinal inflammation causes disorder in bowel motility. Th17 cytokines are involved in intestinal inflammation. To understand the role of interleukin (IL)-17 in intestinal motility, we examined effects of IL-17A on contractile activities of organ-cultured ileum. Rat ileal smooth muscle strips were organ cultured with IL-17A. Muscle contraction was measured, and cells expressing inducible nitric oxide synthase (iNOS) were identified with immunohistochemistry. Creating Th17-transferred colitis model mice, in vivo effects of IL-17 on contractile activities, and iNOS mRNA expression in colonic smooth muscle were investigated. Treatment with IL-17A for 12 h and 3 days attenuated carbachol- and membrane depolarization–induced contractions in organ-cultured rat ileum. NG-Nitro-l-arginine methyl ester (100 μM), a nitric oxide synthase inhibitor, completely reversed the IL-17A–induced inhibition of contractile force. Ileal tissue cultured in the presence of IL-17A showed increased expression of iNOS mRNA and protein. Immunohistochemical analysis using an iNOS antibody revealed that iNOS protein was expressed on ED2-positive muscularis macrophages. The level of iNOS mRNA was also increased in inflamed colonic smooth muscle of Th17-transferred colitis model mice. In intestinal inflammation, IL-17A induces an intestinal motility disorder through iNOS expression in muscularis macrophages.

【 授权许可】

Unknown