Mouse islet cell lysis mediated by interleukin-1-induced Fas (original) (raw)

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This study was conducted to investigate the possible involvement of Fas in β-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 102-105 U/l of mouse interleukin-1 α (IL-1α) 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 103 U/l of IL-1α. Primary islet cells were resistant to an agonistic anti-Fas monoclonal antibody. However, 12 h pretreatment with IL-1α 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-1α 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 NG-monomethyl-l-arginine. β-TC1 cells also expressed Fas mRNA when exposed to IL-1α or IL-1α plus interferon-γ. These observations suggest that Fas-mediated apoptosis may be a mechanism of islet cell death in autoimmune insulitis. [Diabetologia (1996) 39: 1306–1312]

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Authors and Affiliations

1. Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, , , , , , JP
   K. Yamada, N. Takane-Gyotoku, X. Yuan, F. Ichikawa, C. Inada & K. Nonaka

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1. K. Yamada
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2. N. Takane-Gyotoku
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3. X. Yuan
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4. F. Ichikawa
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5. C. Inada
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6. K. Nonaka
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Received: 5 April 1996 and in revised form: 7 August 1996

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Yamada, K., Takane-Gyotoku, N., Yuan, X. et al. Mouse islet cell lysis mediated by interleukin-1-induced Fas.Diabetologia 39, 1306–1312 (1996). https://doi.org/10.1007/s001250050574

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• Issue Date: October 1996
• DOI: https://doi.org/10.1007/s001250050574