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Roles of cholesterol and bile salts in the pathogenesis of gallbladder hypomotility and inflammation: cholecystitis is not caused by cystic duct obstruction



This article is corrected by:

  1. Errata: Corrigendum Volume 25, Issue 6, 547, Article first published online: 14 May 2013

Address for Correspondence

Jose Behar, Division of Gastroenterology Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02902, USA.



Background and Purpose

A large number of human and animal studies have challenged the hypothesis that cystic duct obstruction by gallstones causes cholecystitis. These studies suggest that lithogenic bile that can deliver high cholesterol concentrations to the gallbladder wall causes hypomotility and creates a permissive environment that allows normal concentrations of hydrophobic bile salts to inflame the mucosa and impair muscle function inhibiting gallbladder emptying. High concentrations of cholesterol increase its diffusion rates through the gallbladder wall where they are incorporated into the sarcolemmae of muscle cells by caveolin proteins. High caveolar cholesterol levels inhibit tyrosine-induced phosphorylation of caveolin proteins required to transfer receptor–G protein complexes into recycling endosomes. The sequestration of these receptor–G protein complexes in the caveolae results in fewer receptors recycling to the sarcolemmae to be available for agonist binding. Lower internalization and recycling of CCK-1 and other receptors involved in muscle contraction explain gallbladder hypomotility. PGE2 receptors involved in cytoprotection are similarly affected. Cells with a defective cytoprotection failed to inactivate free radicals induced by normal concentrations of hydrophobic bile salts resulting in chronic inflammation that may lead to acute inflammation. Ursodeoxycholic acid salts (URSO) block these bile salts effects thereby preventing the generation of free radicals in muscle cells in vitro and development of cholecystitis in the ligated common bile duct in guinea pigs in vivo. Treatment with URSO improves muscle contraction and reduces the oxidative stress in patients with symptomatic cholesterol gallstones by lowering cholesterol concentrations and blocking the effects of hydrophobic bile salts on gallbladder tissues.