Ethanol induces 2',5'-oligoadenylate synthetase and antiviral activities through interferon-beta production.
We demonstrate here that ethanol, in contrast to heat shock (Chousterman, S., Chelbi-Alix, M.K., and Thang, M.N. (1987) J. Biol. Chem. 262, 4806-4811), induces interferon (IFN) synthesis and its related activities in Madin-Darby bovine kidney (MDBK) cells. The induced IFN is secreted maximally at 6 h, whereas the induction of 2',5'-oligoadenylate synthetase mRNA peaks between 9 and 12 h and its activity at 15 h. The appearance of both 2',5'-oligoadenylate synthetase activity and the antiviral state upon ethanol treatment is prevented by anti-bovine recombinant IFN-beta antibodies. Bovine diarrhea virus infection-free MDBK cells cultured in medium supplemented with serum substitute also gave similar results, thus indicating that IFN synthesis induced by ethanol is not mediated by the activation of bovine diarrhea virus. Together, these results show that: 1) ethanol induces the 2',5'-oligoadenylate synthetase and antiviral activities through IFN-beta production; and 2) the IFN produced does not act directly from inside the cells, but has to be first secreted to bind to its receptor. In MDBK cells, ethanol induces the synthesis of the 70-kDa protein, which precedes the expression of 2',5'-oligoadenylate synthetase; moreover, the transient nature of the synthesis of the hsp 70 in these cells is similar after both heat shock and ethanol treatment.
Chelbi-Alix
M K
MK
Unité 245 Institut National de la Santé et de la Recherche Médicale, Centre Institut National de la Santé et de la Recherche Médicale Saint-Antoine, Paris, France.
Chousterman
S
S
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D000818:Animals; D000998:Antiviral Agents; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D001908:Diarrhea Viruses, Bovine Viral / Q000502:physiology*; D004790:Enzyme Induction; D000431:Ethanol / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis*; D007700:Kinetics; D008970:Molecular Weight
D000998:Antiviral Agents; D006360:Heat-Shock Proteins; D000431:Ethanol; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase