Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction.
<h4>Background and aim</h4>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.<h4>...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092960&type=printable |
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| author | Hirotada Akiho Yohei Tokita Kazuhiko Nakamura Kazuko Satoh Mitsue Nishiyama Naoko Tsuchiya Kazuaki Tsuchiya Katsuya Ohbuchi Yoichiro Iwakura Eikichi Ihara Ryoichi Takayanagi Masahiro Yamamoto |
| author_facet | Hirotada Akiho Yohei Tokita Kazuhiko Nakamura Kazuko Satoh Mitsue Nishiyama Naoko Tsuchiya Kazuaki Tsuchiya Katsuya Ohbuchi Yoichiro Iwakura Eikichi Ihara Ryoichi Takayanagi Masahiro Yamamoto |
| author_sort | Hirotada Akiho |
| collection | DOAJ |
| description | <h4>Background and aim</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>We propose and discuss the possible involvement of IL-17A and its downstream signaling cascade in SMCs in diarrheal hypermotility in various GI disorders. |
| first_indexed | 2024-12-23T14:11:25Z |
| format | Article |
| id | doaj.art-d20e0878ca5a40838ccfc7563f164b56 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T16:22:31Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-d20e0878ca5a40838ccfc7563f164b562025-02-22T05:32:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9296010.1371/journal.pone.0092960Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction.Hirotada AkihoYohei TokitaKazuhiko NakamuraKazuko SatohMitsue NishiyamaNaoko TsuchiyaKazuaki TsuchiyaKatsuya OhbuchiYoichiro IwakuraEikichi IharaRyoichi TakayanagiMasahiro Yamamoto<h4>Background and aim</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>We propose and discuss the possible involvement of IL-17A and its downstream signaling cascade in SMCs in diarrheal hypermotility in various GI disorders.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092960&type=printable |
| spellingShingle | Hirotada Akiho Yohei Tokita Kazuhiko Nakamura Kazuko Satoh Mitsue Nishiyama Naoko Tsuchiya Kazuaki Tsuchiya Katsuya Ohbuchi Yoichiro Iwakura Eikichi Ihara Ryoichi Takayanagi Masahiro Yamamoto Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. PLoS ONE |
| title | Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. |
| title_full | Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. |
| title_fullStr | Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. |
| title_full_unstemmed | Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. |
| title_short | Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. |
| title_sort | involvement of interleukin 17a induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092960&type=printable |
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