15-deoxy-Δ12,14-prostaglandin J2 is a negative regulator of macrophage functions

15-Deoxy-Delta (12,14)-prostaglandin J(2) (dPGJ(2)) is a bioactive metabolite of the J(2) series that has been identified as a ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). Because PPAR-gamma is highly expressed in macrophages obtained from stimulant-elicited peritonitis, but not in resident peritoneal macrophages, the effect of dPGJ(2) was tested on innate functions of macrophages. dPGJ(2) inhibited adhesion and phagocytosis of Escherichia coli. Inhibition of these functions by dPGJ(2) was not mediated via the adhesion molecule Mac-1. In addition, dPGJ(2) inhibited chemotaxis toward zymosan-activated serum and it also inhibited the production of superoxide anion when macrophages were stimulated with phorbol 12-myristate 13-acetate (PMA) or opsonized zymosan (OPZ), but not lipopolysaccharide. Similarly, dPGJ(2) inhibited the production of hydrogen peroxide when macrophages were stimulated with either PMA or OPZ. These studies suggest that dPGJ(2) may be a negative regulator of macrophage functions. (C) 2001 Elsevier Science B.V. All rights reserved.