| First Author | Yamada K | Year | 1996 |
| Journal | Diabetologia | Volume | 39 |
| Issue | 11 | Pages | 1306-12 |
| PubMed ID | 8932996 | Mgi Jnum | J:36613 |
| Mgi Id | MGI:84040 | Doi | 10.1007/s001250050574 |
| Citation | Yamada K, et al. (1996) Mouse islet cell lysis mediated by interleukin-1-induced Fas. Diabetologia 39(11):1306-12 |
| abstractText | This study was conducted to investigate the possible involvement of Fas in beta-cell death in insulitis of Type 1 (insulin-dependent) diabetes mellitus. Although primary cultured Balb/c mouse islet cells did not express Fas mRNA, 4-12 hours of treatment with 10(2)-10(3) U/l of mouse interleukin-1 alpha (IL-1 alpha) induced the expression of Fas mRNA. Surface Fas expression was detected by immunofluorescence flow cytometry using a non-cytolytic anti-Fas monoclonal antibody after 6 or 12 h of incubation with 10(3) U/l of IL-1 alpha. Primary islet cells were resistant to an agonistic anti-Fas monoclonal antibody. However, 12 h pretreatment with IL-1 alpha sensitized islet cells to its cytolytic effect. Significant cell death was observed 24 h after the addition of anti-Fas, and progressively increased until 72 h, when specific 51Cr release was 72 +/- 6%. Agarose gel electrophoresis of DNA extracted from cells exposed to IL-1 alpha and agonistic anti-Fas showed internucleosomal DNA fragmentation, a hallmark of apoptotic cell death. Since the Fas antibody showed no cross-reactive activity of tumour necrosis factor (TNF), the cytotoxic effect was not mediated by TNF receptors. A protein synthesis inhibitor cycloheximide augmented Fas-mediated islet cell death. The Fas-mediated killing of islet cells was not L-arginine-dependent, or blocked by N(G)-monomethyl-L-arginine. beta-TC1 cells also expressed Fas mRNA when exposed to IL-1 alpha or IL-1 alpha plus interferon-gamma. These observations suggest that Fas-mediated apoptosis may be a mechanism of islet cell death in autoimmune insulitis. |
