title: IL-17A induces hypo-contraction of intestinal smooth muscle via induction of iNOS in muscularis macrophages.
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. N(G)-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.
authors: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan.
authors: Daisuke
authors: D
authors: Mori
authors: Nobumasa
authors: N
authors: Watanabe
authors: Osamu
authors: O
authors: Kaminuma
authors: Takahisa
authors: T
authors: Murata
authors: Takachika
authors: T
authors: Hiroi
authors: Hiroshi
authors: H
authors: Ozaki
authors: Masatoshi
authors: M
authors: Hori
mesh_terms: D000818:Animals; D003092:Colitis / Q000201:enzymology / Q000503:physiopathology; D004195:Disease Models, Animal; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D007082:Ileum / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D020381:Interleukin-17 / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse