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

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Author(s)

    • Mori Daisuke Mori Daisuke
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan
    • Murata Takahisa
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan|Department of Animal Radiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan
    • Hiroi Takachika
    • Department of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science, Japan
    • Ozaki Hiroshi
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan
    • Hori Masatoshi
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan

Abstract

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. <i>N</i><sup>G</sup>-Nitro-<span style="font-variant: small-caps;">l</span>-arginine methyl ester (100 <i>μ</i>M), 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.

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 125(4), 394-405, 2014

    The Japanese Pharmacological Society

Codes

  • NII Article ID (NAID)
    130004677798
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    ENG
  • ISSN
    1347-8613
  • NDL Article ID
    025698817
  • NDL Call No.
    Z53-D199
  • Data Source
    NDL  J-STAGE 
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