Murine pancreatic beta TC3 cells show greater 2', 5'-oligoadenylate synthetase (2'5'AS) antiviral enzyme activity and apoptosis following IFN-alpha or poly(I:C) treatment than pancreatic alpha TC3 cells.
Type 1 diabetes is caused by autoimmune destruction of pancreatic beta cells, possibly virus initiated. Virus infection induces alpha-interferon (IFN-alpha), leading to upregulation of genes encoding double-stranded (ds) RNA-dependent antiviral enzymes 2', 5'-oligoadenylate synthetase (2'5'AS) and PKR (p68). To investigate whether beta cell specificity could be due to antiviral differences between beta and alpha cells, we treated beta and alpha TC3 cell lines with IFN-alpha and/or poly(I:C) (a synthetic dsRNA). Results showed that, following IFN-alpha stimulation, increases in 2'5'AS levels and activities were significantly higher in beta than alpha cells (P < .001), whereas increases in PKR level and activity were comparable in the two cell types. Poly(I:C) stimulated 2'5'AS activity in beta but not alpha cells, and co-transfection IFN-alpha plus poly(I:C) induced apoptosis in beta but not alpha cells. These findings suggest that the elevated 2'5'AS response of pancreatic beta cells could render them particularly vulnerable to damage and/or apoptosis during virus infection.
Li
M
M
Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, 950 W 28th Ave., Vancouver, BC, Canada V5Z 4H4.
Zheng
D-J
DJ
Field
L L
LL
Bonnevie-Nielsen
V
V
D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D050416:Glucagon-Secreting Cells / Q000201:enzymology*; D050417:Insulin-Secreting Cells / Q000201:enzymology*; D016898:Interferon-alpha / Q000494:pharmacology*; D051379:Mice; D011070:Poly I-C / Q000494:pharmacology*; D051196:Toll-Like Receptor 3 / Q000502:physiology; D014777:Virus Diseases / Q000201:enzymology* / Q000473:pathology; D019892:eIF-2 Kinase / Q000032:analysis / Q000378:metabolism
D016898:Interferon-alpha; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D019892:eIF-2 Kinase; D015088:2',5'-Oligoadenylate Synthetase; D011070:Poly I-C