Protective role for cytosolic phospholipase A2α in autoimmune diabetes of mice

Cytosolic phospholipase A2α (cPLA2α) plays an important role in arachidonate pathway. To investigate the contribution of cPLA2α to autoimmune diabetes, we established non-obese diabetic (NOD) mouse, an excellent model for human type 1 diabetes, deficient in cPLA2α. These mice showed severe insulitis and a higher incidence of diabetes. In their macrophages, decreased prostaglandin E2 (PGE2) induced by cPLA2α deficiency, and the increase in production of tumor necrosis factor (TNF)-α were observed. These results suggested that cPLA2α plays a protective role in progression of insulitis and development of autoimmune diabetes by suppression of TNF-α production from macrophages.