Cytokine synergism in apoptosis: its role in diabetes and cancer.
The effects of individual cytokine on apoptosis have been extensively studied. However, the effect of the cytokine combination, or the synergistic effect of cytokines on cell death, has not been widely studied, though synergism between cytokines has been documented in a variety of biological situations. In our effort to identify the final death effector molecule(s) in autoimmune diabetes, we inadvertently became interested in the cytokine synergism. We discovered that IFNgamma/TNFalpha synergism, rather than the Fas ligand as currently believed, is responsible for the apoptosis of pancreatic islet cells both in vitro and in vivo. We also studied similar cytokine synergism in cancer cell deaths, and noted the similarities and dissimilarities between cancer cell death and islet cell death.
Lee
Myung-Shik
MS
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine and National Research Laboratory of Cell Death and Diabetes Research, Seoul 135-710, Korea. mslee@smc.samsung.co.kr
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000378:metabolism; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein; D006801:Humans; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma