Prostaglandin E2 Amplifies Cytosolic Phospholipase A2- and Cyclooxygenase-2-dependent Delayed Prostaglandin E2 Generation in Mouse Osteoblastic Cells

The Functions of Five Distinct Mammalian Phospholipase A2s in Regulating Arachidonic Acid Release

“…The simplest explanation for these events is that sPLA 2 s-IIA and -V activate intracellular cPLA 2 , which eventually releases AA in a selective manner. Indeed, this route is compatible with the recent studies using rat mesangial cells (77), human neutrophils (78), human astrocytoma (79), and mouse osteoblasts (19), in which sPLA 2 -IIA caused translational (19) or post-translational (77-79) activation of cPLA 2 , probably through the production of lipid mediators (19,77,78) or through the putative sPLA 2 receptor-dependent and catalysis-independent process (79). However, several lines of evidence argue against this speculation in our 293 cell system.…”

“…The studies using cPLA 2 inhibitors, which suppressed AA release by cPLA 2 and by sPLA 2 s-IIA and -V transformants to a similar extent, support the previously proposed hypothesis that endogenous cPLA 2 is required for sPLA 2 s to exert their functions (15,19,20,58). Conversely, the sPLA 2 -IIA inhibitor showed no inhibitory effect on cPLA 2 -mediated AA release, indicating that sPLA 2 -IIA is not needed for the action of cPLA 2 .…”

“…The AA thus liberated is supplied to constitutive COX-1 and 5-lipoxygenase to be converted into prostanoids and leukotrienes, respectively (30 -33). cPLA 2 has also been implicated in delayed, COX-2-dependent prostanoid generation lasting for hours despite the absence of Ca 2ϩ signaling in this setting (15,19,34,35), although in some experimental systems cPLA 2 failed to supply AA to COX-2 during the delayed response unless the cells were exposed to a secondary Ca 2ϩ -mobilizing stimulus (36,37). Increased expression of cPLA 2 induced by proinflammatory stimuli has been reported to be linked to an ongoing delayed response (19,34,35,38) or to priming for increased immediate response (21,36,37,39,40).…”

Prostaglandin Levels in Stimulated Macrophages Are Controlled by Phospholipase A2-activating Protein and by Activation of Phospholipase C and D

“…Several groups (15)(16)(17)(18)(19)(20) have reported that sPLA 2 is the primary phospholipase involved in PG production in target cells. Conversely, other investigators have documented that cPLA 2 is the predominant phospholipase involved in PG formation (13,(21)(22)(23)(24)(25)(26)(27). The contribution of the other phospholipases (PLC and PLD) in PG production has not been as extensively studied (28).…”

“…PGE 2 has been shown to increase cPLA 2 and COX-2 levels and thereby amplify its own production, as well as to increase synthesis of some inflammatory cytokines resulting in a perpetuation of the immune response (23,41,42).…”