Apoptosis of human islet cells by cytokines.
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.
New Experimental Therapeutics Branch, Division of Convergence Technology, National Cancer Center, Goyang 410-769, Korea.
Sunshin
S
Kim
Kyoung-Ah
KA
Kim
Kyoungho
K
Suk
Yun-Hee
YH
Kim
Seung Hoon
SH
Oh
Moon-Kyu
MK
Lee
Kwang-Won
KW
Kim
Myung-Shik
MS
Lee