Differential responsiveness to interferon-alpha in beta-cells and non-beta cells.
Interferon-alpha (IFN-alpha) is important in the innate immune defense, particularly in viral infections. IFN-alpha induces 2',5'A synthetase, the products of which, 2',5'-oligoadenine nucleotides, activate mRNA degrading enzymes. IFN-alpha is the first detectable cytokine in the insulitis lesion seen in recent-onset IDDM, and insulin promoter directed expression of IFN-alpha in transgenic mice leads to development of IDDM. Here, we demonstrate that IFN-alpha induces 2',5'A synthetase activity only in insulin-producing betaTC3 cells and in isolated single rat beta-cells but not in alphaTC3 cells or in isolated rat non-beta-cells. The increased responsiveness of beta-cells but not non-beta-cells to IFN-alpha with the ensuing activation of the mRNA-degrading 2',5'A synthetase system suggests why only the beta-cells are destroyed in the diabetogenic process.
Bonnevie-Nielsen
V
V
Department of Medical Microbiology, Odense University, Denmark.
Buschard
K
K
Dyrberg
T
T
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D004790:Enzyme Induction; D015870:Gene Expression; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics; D016898:Interferon-alpha / Q000096:biosynthesis / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011070:Poly I-C / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012330:RNA, Double-Stranded / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D007328:Insulin; D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D015088:2',5'-Oligoadenylate Synthetase; D011070:Poly I-C