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Effect of tumor necrosis factor α on intrahepatic bile duct epithelial cell of rat liver
Author(s) -
Mano Y,
Ishii M,
Okamoto H,
Igarashi T,
Kobayashi K,
Toyota T
Publication year - 1996
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510230642
Subject(s) - trypan blue , tumor necrosis factor alpha , tight junction , lactate dehydrogenase , cytokine , necrosis , bile duct , intrahepatic bile ducts , medicine , pathology , horseradish peroxidase , biology , endocrinology , cell , microbiology and biotechnology , biochemistry , enzyme
Tumor necrosis factor α (TNF‐α), which is primarily produced by macrophages, is a cytokine with various biological activities. Macrophage infiltration often accompanies experimental cholangitis in rats, and chronic cholangitis in humans. The pathophysiologic significance of TNF‐α in cholangitis is not known. We used cultured, polarized intrahepatic bile duct epithelial cells (IBDECs) from rat liver to determine whether TNF‐α directly affects the organization of IBDEC monolayers. The addition of recombinant TNF‐α (rTNF‐α) to culture media at concentrations from 10 to 200 U/mL lacked cytotoxicity to the IBDECs as judged by trypan blue exclusion and lactate dehydrogenase (LDH) release. rTNF‐α transiently reduced transepithelial electrical resistance in a dose‐dependent manner. During this decrease in resistance, the cellular tight junctions became leaky, allowing horseradish peroxidase (HRP) penetration. rTNF‐α, at concentrations up to 200 U/mL, did not detach IBDECs from Matrigel, an artificial basement membrane. Electron microscopy and immunohistochemistry for F‐actin showed a well‐preserved cell structure and organization of IBDECs. Results suggest that TNF‐α is nontoxic to IBDECs, and that it increases the permeability of tight junctions. TNF‐α may thus disturb the barrier function of the bile duct.