Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction

Hirotada Akiho, Yohei Tokita, Kazuhiko Nakamura, Kazuko Satoh, Mitsue Nishiyama, Naoko Tsuchiya, Kazuaki Tsuchiya, Katsuya Ohbuchi, Yoichiro Iwakura, Eikichi Ihara, Ryoichi Takayanagi, Masahiro Yamamoto

研究成果: ジャーナルへの寄稿記事

6 引用 (Scopus)

抄録

Background and Aim: 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. Methods: 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. Results: 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. Conclusions: We propose and discuss the possible involvement of IL-17A and its downstream signaling cascade in SMCs in diarrheal hypermotility in various GI disorders.

元の言語英語
記事番号e92960
ジャーナルPloS one
9
発行部数5
DOI
出版物ステータス出版済み - 5 5 2014

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Interleukin-17
smooth muscle
myocytes
Smooth Muscle Myocytes
Muscle
digestive system
Cells
T-cells
Enteritis
Chemical activation
enteritis
mitogen-activated protein kinase
T-lymphocytes
Gq-G11 GTP-Binding Protein alpha Subunits
GTP-Binding Protein Regulators
Gastrointestinal Transit
gastrointestinal transit
myosin light chains
T-Lymphocytes
gastrointestinal motility

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

これを引用

Akiho, H., Tokita, Y., Nakamura, K., Satoh, K., Nishiyama, M., Tsuchiya, N., ... Yamamoto, M. (2014). Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. PloS one, 9(5), [e92960]. https://doi.org/10.1371/journal.pone.0092960

Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. / Akiho, Hirotada; Tokita, Yohei; Nakamura, Kazuhiko; Satoh, Kazuko; Nishiyama, Mitsue; Tsuchiya, Naoko; Tsuchiya, Kazuaki; Ohbuchi, Katsuya; Iwakura, Yoichiro; Ihara, Eikichi; Takayanagi, Ryoichi; Yamamoto, Masahiro.

:: PloS one, 巻 9, 番号 5, e92960, 05.05.2014.

研究成果: ジャーナルへの寄稿記事

Akiho, H, Tokita, Y, Nakamura, K, Satoh, K, Nishiyama, M, Tsuchiya, N, Tsuchiya, K, Ohbuchi, K, Iwakura, Y, Ihara, E, Takayanagi, R & Yamamoto, M 2014, 'Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction', PloS one, 巻. 9, 番号 5, e92960. https://doi.org/10.1371/journal.pone.0092960
Akiho, Hirotada ; Tokita, Yohei ; Nakamura, Kazuhiko ; Satoh, Kazuko ; Nishiyama, Mitsue ; Tsuchiya, Naoko ; Tsuchiya, Kazuaki ; Ohbuchi, Katsuya ; Iwakura, Yoichiro ; Ihara, Eikichi ; Takayanagi, Ryoichi ; Yamamoto, Masahiro. / Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. :: PloS one. 2014 ; 巻 9, 番号 5.
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abstract = "Background and Aim: 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. Methods: 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. Results: 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. Conclusions: We propose and discuss the possible involvement of IL-17A and its downstream signaling cascade in SMCs in diarrheal hypermotility in various GI disorders.",
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AU - Akiho, Hirotada

AU - Tokita, Yohei

AU - Nakamura, Kazuhiko

AU - Satoh, Kazuko

AU - Nishiyama, Mitsue

AU - Tsuchiya, Naoko

AU - Tsuchiya, Kazuaki

AU - Ohbuchi, Katsuya

AU - Iwakura, Yoichiro

AU - Ihara, Eikichi

AU - Takayanagi, Ryoichi

AU - Yamamoto, Masahiro

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AB - Background and Aim: 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. Methods: 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. Results: 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. Conclusions: We propose and discuss the possible involvement of IL-17A and its downstream signaling cascade in SMCs in diarrheal hypermotility in various GI disorders.

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