15-deoxy-delta(12-14)-prostaglandin-j2 and Peritonitis

15-Deoxy-delta(12,14)-prostaglandin J2 (dPGJ2) is a bioactive metabolite of the J2 series that has been identified as a ligand for peroxisome proliferator-activated receptor gamma (PPARgamma). Because PPARgamma is highly expressed in macrophages obtained from stimulant-elicited peritonitis, but not in resident peritoneal macrophages, the effect of dPGJ2 was tested on innate functions of macrophages. dPGJ2 inhibited adhesion and phagocytosis of Escherichia coli. Inhibition of these functions by dPGJ2 was not mediated via the adhesion molecule Mac-1. In addition, dPGJ2 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, dPGJ2 inhibited the production of hydrogen peroxide when macrophages were stimulated with either PMA or OPZ. These studies suggest that dPGJ2 may be a negative regulator of macrophage functions.

Topics: Animals; Cell Adhesion; Chemotaxis; Escherichia coli; Hydrogen Peroxide; Inflammation; Ligands; Lipopolysaccharides; Macrophage-1 Antigen; Macrophages, Peritoneal; Male; Oxidative Stress; Peritonitis; Phagocytosis; Prostaglandin D2; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear; Superoxides; Tetradecanoylphorbol Acetate; Transcription Factors; Zymosan