ISLET EXPRESSION OF PERFORIN, FAS APO-1 AND INTERLEUKIN-1 CONVERTING-ENZYME (ICE) IN NONOBESE DIABETIC (NOD) MICE/

The aim of the present study was to correlate the islet expression of the apoptosis-associated factors Fas/Apo-1, Fast, ICE and perforin wit h the progression of P-cell destruction in non-obese diabetic (NOD) mi ce. For this purpose, thymus and isolated pancreatic islets from male and female NOD mice of 5 and 15 weeks of age were subjected to immunob lot analysis. Islet expression of the Fas/Apo-1 receptor and ICE were increased in islets from female mice 15 weeks of age as compared to co rresponding males. No Fas/Apo-l or ICE signal was observed in the 5-we ek-old mice. The expression of perforin increased both in islets and i n thymus with age and female gender. Islet expression of Fast could no t be detected. Culture of isolated islets from NMRI mice in the presen ce of interleukin-1 beta (IL-1 beta) induced the expression of ICE. Ho wever, addition of Fas-activating antibody, either alone or in combina tion with IL-1 beta, to isolated islets did not induce DNA fragmentati on. The present results support a direct role of the Fas/FasL and the perforin systems in the autoimmune destruction of insulin producing ce lls. (C) 1998 Elsevier Science B.V. All rights reserved.