TY - JOUR
T1 - Inflammatory Cytokines Alter Human Gallbladder Epithelial Cell Absorption/Secretion
AU - Rege, Robert V
N1 - Funding Information:
From the Division of Gastrointestinal and Endocrine SurgeD; UniversiTt of Texas Southwestern Medical Center, Dallas, Tex. Supported by a Merit Review Award from the Research Division of the Department of Veteran's Affa,rs. Presented m part at the Fortieth ,Annual Meeting of The Society for Surge D-of the ~MimentaryT ract, Orlando, Fla., May l 6-19, 1999. Reprmt requests: Robert V. Rege, M.D., Professor and Chairman, Dlvlsmn of Gastrointestinal and Endocrine Surgen., University of Texas Southwestern Medical Center, 5323 Har D" Hines Blvd., Dallas, TX 75235-9156. e-mail: rrege@mednet.swnet.edu
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Gallbladder absorption
KW - Gallbladder secretion
KW - Inflammatory cytokines
KW - Interleukin-1
KW - Tumor necrosis factor
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U2 - 10.1016/S1091-255X(00)80055-4
DO - 10.1016/S1091-255X(00)80055-4
M3 - Article
C2 - 10675242
AN - SCOPUS:0034145536
SN - 1091-255X
VL - 4
SP - 185
EP - 192
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
IS - 2
ER -