Anti- and proinflammatory effects of 15-deoxy-delta-prostaglandin J2(15d-PGJ2) on human eosinophil functions.

The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is recognized as a potent lipid mediator that is derived from PGD(2), which is produced abundantly in allergic inflammatory sites. It is now established that 15d-PGJ(2) negatively regulates cellular functions through its intracellular targets such as peroxisome proliferator-activated receptor-gamma (PPARgamma). However, recent studies revealed that 15d-PGJ(2) appears to possess not only anti-inflammatory activities but also a proinflammatory potential depending on its concentration and the activation state of the target cell. For instance, at low concentrations, 15d-PGJ(2) enhances eotaxin-induced chemotaxis, shape change, and actin reorganization in eosinophils through its ligation with PPARgamma. Moreover, 15d-PGJ(2) itself is a potent chemoattractant, and it induces calcium mobilization, and up-regulates CD11b expression through its membrane receptor--chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Conversely, at high concentrations, 15d-PGJ(2) inhibits eosinophil survival by inducing apoptosis in a PPARgamma-independent manner. Here, we discuss the pathophysiological roles of 15d-PGJ(2) that could act as a paracrine, autocrine, and intracrine substance to regulate eosinophil functions.