| First Author | Ohama T | Year | 2007 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 292 |
| Issue | 5 | Pages | G1429-38 |
| PubMed ID | 17307724 | Mgi Jnum | J:122632 |
| Mgi Id | MGI:3714899 | Doi | 10.1152/ajpgi.00315.2006 |
| Citation | Ohama T, et al. (2007) Intestinal inflammation downregulates smooth muscle CPI-17 through induction of TNF-alpha and causes motility disorders. Am J Physiol Gastrointest Liver Physiol 292(5):G1429-38 |
| abstractText | Motility disorders are frequently observed in intestinal inflammation. We previously reported that in vitro treatment of intestinal smooth muscle tissue with IL-1beta decreases the expression of CPI-17, an endogenous inhibitory protein of smooth muscle serine/threonine protein phosphatase, thereby inhibiting contraction. The present study was performed to examine the pathophysiological importance of CPI-17 expression in the motility disorders by using an in vivo model of intestinal inflammation and to define the regulatory mechanism of CPI-17 expression by proinflammatory cytokines. After the induction of acute ileitis with 2,4,6,-trinitrobenzensulfonic acid, CPI-17 expression declined in a time-dependent manner. This decrease in CPI-17 expression was parallel with the reduction of cholinergic agonist-induced contraction of smooth muscle strips and sensitivity of permeabilized smooth muscle fibers to Ca(2+). Among the various proinflammatory cytokines tested, TNF-alpha and IL-1beta were observed to directly inhibit CPI-17 expression and contraction in cultured rat intestinal tissue. Moreover, both TNF-alpha and IL-1beta inhibited CPI-17 expression and contraction of smooth muscle tissue isolated from wild-type and IL-1alpha/beta double-knockout mice. However, IL-1beta treatment failed to inhibit CPI-17 expression and contraction in TNF-alpha knockout mice. In beta-escin-permeabilized ileal tissues, pretreatment with anti-phosphorylated CPI-17 antibody inhibited the carbachol-induced Ca(2+) sensitization in the presence of GTP. These findings suggest that CPI-17 was downregulated during intestinal inflammation and that TNF-alpha plays a central role in this process. Downregulation of CPI-17 may play a role in motility impairments in inflammation. |
