IL-17A Induces Hypo-contraction of Intestinal Smooth Muscle via Induction of iNOS in Muscularis Macrophages
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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 of Pharmacological Sciences
Journal of Pharmacological Sciences 125(4), 394-405, 2014
The Japanese Pharmacological Society