@entity3426 , @entity3692 and XXXX increase vulnerability of pancreatic beta cells to autoimmune destruction.

@entity3692 @entity6 @entity39 @entity1505 @entity842 @entity3426 @entity35 @entity413 @entity1590
In the pathogenesis of type-1 @entity6 insulin-producing beta-cells are destroyed by cellular autoimmune processes. The locality of beta-cell destruction is the inflamed pancreatic islet. During insulitis cytokines released from islet-infiltrating mononuclear cells affect beta-cells at several levels. We investigated whether cytokine-induced beta-cell destruction is associated with changes in the expression of the surface receptors intercellular adhesion molecule (ICAM)-1 and Fas. Islets from @entity6 -resistant BB @entity35 were exposed to @entity3426 alone or in combination with @entity3692 plus tumour @entity39 factor ( @entity1505 . Cytokines decreased islet insulin content, suppressed @entity413 stimulated insulin secretion and generated enhanced amounts of @entity842 and DNA-strand breaks. While no membrane alterations of @entity3426 treated islets cells were detectable, the cytokine combination caused damage of cell membranes. Independent of @entity6 susceptibility @entity3426 treated islet beta-cells expressed a significantly increased amount of @entity1590 on their surfaces which was not further increased by @entity3692 + @entity1505 . However, @entity3426 induced Fas expression was significantly enhanced only on beta-cells from @entity6 -prone BB @entity35 . From these results we suggest that @entity3426 mediates the major stimulus for @entity1590 induction which is possibly a necessary but not sufficient step in the process of beta-cell destruction. Obviously, the additional enhancement of Fas expression on the surface of beta-cells is important for destruction. The combined action of all three cytokines induced the expression of Fas on the beta-cell surface independent of @entity6 susceptibility, indicating that such a strong stimulus in vitro may induce processes different from the precise mechanisms of beta-cell destruction in vivo.
