Role of caspases in TNF-mediated regulation of cPLA(2).

A major part of the proinflammatory activity of tumor necrosis factor (TNF) is brought about by cytosolic phospholipase A(2) (cPLA(2)) that generates arachidonic acid, the precursor for the production of leukotrienes and prostaglandins. The activation of cPLA(2) and induction of proinflammatory lipid mediators is in striking contrast to the teleologic meaning of apoptosis, which is to avoid an inflammatory reaction. In this review we highlight the evidence for a caspase-mediated cleavage and inactivation of cPLA(2), which seems to be an important mechanism by which TNF downregulates cPLA(2) activity in cells undergoing apoptosis.