Effect of tumor necrosis factor alpha on intrahepatic bile duct epithelial cell of rat liver.
Tumor necrosis factor alpha (TNF-alpha), 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-alpha in cholangitis is not known. We used cultured, polarized intrahepatic bile duct epithelial cells (IBDECs) from rat liver to determine whether TNF-alpha directly affects the organization of IBDEC monolayers. The addition of recombinant TNF-alpha (rTNF-alpha) 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-alpha 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-alpha, 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-alpha is nontoxic to IBDECs, and that it increases the permeability of tight junctions. TNF-alpha may thus disturb the barrier function of the bile duct.
Mano
Y
Y
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ishii
M
M
Okamoto
H
H
Igarashi
T
T
Kobayashi
K
K
Toyota
T
T
D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D017097:Electric Impedance; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha