IL-1beta signaling in cat lower esophageal sphincter circular muscle

American Journal of Physiology. Gastrointestinal and Liver Physiology
Weibiao CaoKaren M Harnett

Abstract

In a cat model of acute experimental esophagitis, resting in vivo lower esophageal sphincter (LES) pressure and in vitro tone are lower than in normal LES, and the LES circular smooth muscle layer contains elevated levels of IL-1beta that decrease the LES tone of normal cats. We now examined the mechanisms of IL-1beta-induced reduction in LES tone. IL-1beta significantly reduced acetylcholine-induced Ca(2+) release in Ca(2+)-free medium, and this effect was partially reversed by catalase, demonstrating a role of H(2)O(2) in these changes. IL-1beta significantly increased the production of H(2)O(2), and the increase was blocked by the p38 MAPK inhibitor SB-203580, by the cytosolic phospholipase A(2) (cPLA(2)) inhibitor AACOCF3, and by the NADPH oxidase inhibitor apocynin, but not by the MEK1 inhibitor PD-98059. IL-1beta significantly increased the phosphorylation of p38 MAPK and cPLA(2). IL-1beta-induced cPLA(2) phosphorylation was blocked by SB-203580 but not by AACOCF3, suggesting sequential activation of p38 MAPK-phosphorylating cPLA(2). The IL-1beta-induced reduction in LES tone was partially reversed by AACOCF3 and by the Ca(2+)-insensitive PLA(2) inhibitor bromoenol lactone (BEL). IL-1beta significantly increased cyclooxyg...Continue Reading

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Citations

Jul 25, 2009·American Journal of Physiology. Cell Physiology·Wei LiMichael B Reid
May 13, 2014·Gastroenterology Clinics of North America·Edaire ChengStuart Jon Spechler
Dec 7, 2007·Gastrointestinal Endoscopy Clinics of North America·Seema S AcevesStuart Jon Spechler
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Nov 15, 2011·Archives of Pharmacal Research·Sun Young ParkUy Dong Sohn
Oct 10, 2020·Prostaglandins & Other Lipid Mediators·A HeeneyD C Winter

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