Journal article

Transmembrane TNF and IFN gamma induce caspase-independent death of primary mouse pancreatic beta cells

W Irawaty, TWH Kay, HE Thomas



Tumor necrosis factor (TNF) is important in the pathogenesis of autoimmune diabetes. It has an important role in immunological and inflammatory processes, and has also been shown to induce apoptotic cell death. We have shown that TNF + IFNgamma induce islet cell death in vitro. TNF exists as a biologically active transmembrane molecule (tmTNF), which is then cleaved to form soluble TNF (sTNF). We reasoned that sTNF, which has been used in previous studies, may not represent TNF in its physiological form. We compared the contributions of caspase activation and nitric oxide production to beta cell death induced by either tmTNF or sTNF together with IFNgamma. CHO cells transfected with a mutate..

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University of Melbourne Researchers