Tumor necrosis factor-alpha internalization and degradation by isolated hepatocytes of rats exposed to ethanol.
Internalization and degradation of human recombinant [125I]TNF-alpha was studied in hepatocytes isolated from rats exposed to ethanol (EtOH) either acutely (i.p. injection, 2.2 g kg(-1) b.wt.) or chronically (14-16 weeks of EtOH feeding in liquid diet). Both acute and chronic EtOH exposure diminished cytokine binding to the cell-surface receptors. In the acute group, EtOH increased internalization of the cytokine, accelerated its disappearance from the cell surface, and markedly reduced its conversion into acid-soluble 125I-containing compounds. In the chronic group, EtOH did not markedly affect these parameters. Internalization and degradation of the cytokine in the chronic group was much lower than in the acute group. It is concluded that EtOH interferes not only with the cytokine binding to the cell-surface receptors, as demonstrated in previous studies, but also with postbinding events, such as internalization and intracellular degradation of TNF-alpha. Possible mechanisms of action of EtOH are discussed.
Deaciuc
I V
IV
Department of Medicine, Gastroenterology, College of Medicine, University of Kentucky, and VA Medical Center, Lexington 40536-0084, USA.
Alappat
J M
JM
D'Souza
N B
NB
Van Thiel
D H
DH
McClain
C J
CJ
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D017077:Culture Media, Conditioned; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D017077:Culture Media, Conditioned; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol