Apoptosis of Human Islet Cells by Cytokines.
- Author:
Sunshin KIM
1
;
Kyoung Ah KIM
;
Kyoungho SUK
;
Yun Hee KIM
;
Seung Hoon OH
;
Moon Kyu LEE
;
Kwang Won KIM
;
Myung Shik LEE
Author Information
- Publication Type:Brief Communication
- Keywords: Diabetes; Apoptosis; Autoimmunity; Cytokines; Inflammatory mediators
- MeSH: Animals; Apoptosis; Autoimmunity; Cytokines; Diabetes Mellitus, Type 1; Humans; Insulinoma; Interleukin-1; Islets of Langerhans; Mice; Mice, Inbred NOD; Perforin; Tumor Necrosis Factor-alpha
- From:Immune Network 2012;12(3):113-117
- CountryRepublic of Korea
- Language:English
- Abstract: FasL, perforin, TNFalpha, IL-1 and NO have been considered as effector molecule(s) leading to beta-cell death in autoimmune diabetes. However, the real culprit(s) of beta-cell destruction have long been elusive despite intense investigation. Previously we have suggested IFNgamma/TNFalpha synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of IFNgamma and TNFalpha but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. IFNgamma treatment conferred susceptibility to TNFalpha-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that IFNgamma/TNFalpha synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by IFNgamma treatment in human islet cells. Taken together, we suggest that IFNgamma/TNFalpha synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.
