| First Author | Akiho H | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 5 | Pages | e92960 |
| PubMed ID | 24796324 | Mgi Jnum | J:217230 |
| Mgi Id | MGI:5613423 | Doi | 10.1371/journal.pone.0092960 |
| Citation | Akiho H, et al. (2014) Involvement of interleukin-17A-induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. PLoS One 9(5):e92960 |
| abstractText | 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, IkappaBzeta- 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 Galphaq/11 protein, has been suggested to be involved in IL-17A-induced hypercontractility. The opposite effect of L-1beta was mediated by IkappaBzeta 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. |
