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KMID : 0923620120120030113
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Immune Network
2012 Volume.12 No. 3 p.113 ~ p.117
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Apoptosis of Human Islet Cells by Cytokines
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Kim Sun-Shin
Kim Kyoung-Ah
Suk Kyoung-Ho
Kim Yun-Hee
Oh Seung-Hoon
Lee Moon-Kyu
Kim Kwang-Won
Lee Myung-Shik
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Abstract
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FasL, perforin, TNF?, IL-1 and NO have been considered as effector molecule(s) leading to ?-cell death in autoimmune diabetes. However, the real culprit(s) of ?-cell destruction have long been elusive despite intense investigation. Previously we have suggested IFN?/TNF? synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of IFN? and TNF? but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. IFN? treatment conferred susceptibility to TNF?-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that IFN?/ TNF? synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by IFN? treatment in human islet cells. Taken together, we suggest that IFN?/TNF? synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.
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KEYWORD
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Diabetes, Apoptosis, Autoimmunity, Cytokines, Inflammatory mediators
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