Effect of Tumor Necrosis Factor α on Intrahepatic Bile Duct Epithelial Cell of Rat Liver

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Abstract
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.

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