Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2

✍ Scribed by H. Iwahashi; T. Hanafusa; Y. Eguchi; H. Nakajima; J. Miyagawa; N. Itoh; K. Tomita; M. Namba; M. Kuwajima; T. Noguchi; Y. Tsujimoto; Y. Matsuzawa

• Publisher: Springer
• Year: 1996
• Tongue: English
• Weight: 819 KB
• Volume: 39
• Category: Article
• ISSN: 0012-186X
• DOI: 10.1007/bf00403299

✦ Synopsis

Cytokines are thought to contribute to the induction of pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. The molecular mechanisms that underlie beta-cell death were investigated by studying cytokine-induced cell death in beta-cell lines. A combination of three cytokines (interleukin-l[3, tumour necrosis factor-s, and interferon-y) induced apoptotic cell death in the mouse pancreatic beta-cell line ~TC1, as judged from the appearance of cells with hypodiploid nuclei and oligonucleosomal DNA fragmentation. The same treatment also induced apoptosis in the mouse pancreatic alpha-cell line aTC1 and the NOD/Lt mouse beta-cell line NIT-l, although to a lesser extent than in ~TC1 cells. The abundance of endogenous Bcl-2 in ~TC1 cells was lower than that in the other two cell lines. Overexpression of human Bcl-2 in ~TC1 cells partially protected them from cytokine-induced cell death. These results suggest that apoptosis may be responsible, at least in part, for cytokine-induced beta-cell destruction and that Bcl-2 prevents apoptosis in pancreatic islet cells. [Diabetologia (1996) 39: 530-536] Kel~ords Pancreatic beta cell, Bcl-2, apoptosis, cytokine, interleukin-1, tumour necrosis factor, interferon-y.