Inflammatory Cytokines Alter Human Gallbladder Epithelial Cell Absorption/Secretion

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Gallbladder inflammation is an early feature of gallstone formation in animal models. The inflammatory response is associated with increases in myeloperoxidase and interleukin (IL)-1 activities in the gallbladder wall. The present studies were designed to determine whether inflammatory cytokines directly affect gallbladder epithelial cell absorptive function. Studies were performed using cultured human gallbladder epithelial cells derived from a well-differentiated gallbladder carcinoma. Confluent monolayers were exposed to interleukin-1 (IL-1α), IL-1α plus its specific receptor inhibitor IL-1ra, tumor necrosis factor (TNF-α), lipopolysaccharide, or prostaglandin E2. Unidirectional sodium and chloride fluxes were measured and used to calculate net ion fluxes. Compared to control monolayers, lipopolysaccharide, prostaglandin E2, IL-1α, and TNF-α decreased mucosal-to-serosal and net sodium and chloride fluxes and increased scrosal-to-mucosal movement of sodium and unmeasured ions. The effects of IL-1α were completely inhibited by its specific receptor antagonist IL-1ra. Similar to the proinflammatory agents lipopolysaccharide and prostaglandin E2, the inflammatory cytokines IL-1α and TNF-α directly affected gallbladder epithelial cell absorptive function. Because normal gallbladder absorptive function is protective against gallstone formation, alterations in absorptive function due to inflammation in the gallbladder wall may play a role in gallstone pathogenesis.

Original languageEnglish (US)
Pages (from-to)185-192
Number of pages8
JournalJournal of Gastrointestinal Surgery
Volume4
Issue number2
DOIs
StatePublished - Jan 1 2000

Keywords

  • Gallbladder absorption
  • Gallbladder secretion
  • Inflammatory cytokines
  • Interleukin-1
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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