Apoptosis of Human Islet Cells by Cytokines

• Published in: Immune network Vol. 12; no. 3; pp. 113 - 117
• Main Authors: Kim, Sun-Shin, Kim, Kyoung-Ah, Suk, Kyoung-Ho, Kim, Yun-Hee, Oh, Seung-Hoon, Lee, Moon-Kyu, Kim, Kwang-Won, Lee, Myung-Shik
• Format: Journal Article
• Language: English
• Published: Korea (South) 대한면역학회 01.06.2012; The Korean Association of Immunologists
• Subjects: Brief Communication; 면역학; Autoimmunity; Diabetes; Inflammatory mediators; Cytokines; Apoptosis
• ISSN: 1598-2629; 2092-6685; 2092-6685
• DOI: 10.4110/in.2012.12.3.113

FasL, perforin, TNFα, IL-1 and NO have been considered as effector molecule(s) leading to β-cell death in autoimmune diabetes. However, the real culprit(s) of β-cell destruction have long been elusive despite intense investigation. Previously we have suggested IFNγ/TNFα synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of IFNγ and TNFα but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. IFNγ treatment conferred susceptibility to TNFα-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that IFNγ/TNFα synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by IFNγ treatment in human islet cells. Taken together, we suggest that IFNγ/TNFα synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.