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题目:: Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction.
作者:: Akiho(Hirotada),Tokita(Yohei),Nakamura(Kazuhiko),Satoh(Kazuko),Nishiyama(Mitsue),Tsuchiya(Naoko),Tsuchiya(Kazuaki),Ohbuchi(Katsuya),Iwakura(Yoichiro),Ihara(Eikichi),Takayanagi(Ryoichi),Yamamoto(Masahiro)
状态:: 发布时间2014-05-06 , 更新时间 2015-08-06
期刊:: PLoS One
摘要:: The etiology of post-inflammatory gastrointestinal (GI) motility dysfunction, after resolution of acute symptoms of inflammatory bowel diseases (IBD) and intestinal infection, is largely unknown, however, a possible involvement of T cells is suggested.,Using the mouse model of T cell activation-induced enteritis, we investigated whether enhancement of smooth muscle cell (SMC) contraction by interleukin (IL)-17A is involved in postinflammatory GI hypermotility.,Activation of CD3 induces temporal enteritis with GI hypomotility in the midst of, and hypermotility after resolution of, intestinal inflammation. Prolonged upregulation of IL-17A was prominent and IL-17A injection directly enhanced GI transit and contractility of intestinal strips. Postinflammatory hypermotility was not observed in IL-17A-deficient mice. Incubation of a muscle strip and SMCs with IL-17A in vitro resulted in enhanced contractility with increased phosphorylation of Ser19 in myosin light chain 2 (p-MLC), a surrogate marker as well as a critical mechanistic factor of SMC contractility. Using primary cultured murine and human intestinal SMCs, IκBζ- and p38 mitogen-activated protein kinase (p38MAPK)-mediated downregulation of the regulator of G protein signaling 4 (RGS4), which suppresses muscarinic signaling of contraction by promoting inactivation/desensitization of Gαq/11 protein, has been suggested to be involved in IL-17A-induced hypercontractility. The opposite effect of L-1β was mediated by IκBζ and c-jun N-terminal kinase (JNK) activation.,We propose and discuss the possible involvement of IL-17A and its downstream signaling cascade in SMCs in diarrheal hypermotility in various GI disorders.
语言:: eng
DOI:

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