Peroxisome proliferator-activated receptor-gamma ligand, 15-deoxy-Delta12,14-prostaglandin J2, reduces neutrophil migration via a nitric oxide pathway

J Immunol. 2008 Jan 1;180(1):609-17. doi: 10.4049/jimmunol.180.1.609.


Ligands for peroxisome proliferator-activated receptor gamma (PPAR-gamma), such as 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) have been implicated as a new class of anti-inflammatory compounds with possible clinical applications. Based on this concept, this investigation was designed to determine the effect of 15d-PGJ2-mediated activation of PPAR-gamma ligand on neutrophil migration after an inflammatory stimulus and clarify the underlying molecular mechanisms using a mouse model of peritonitis. Our results demonstrated that 15d-PGJ2 administration decreases leukocyte rolling and adhesion to the inflamed mesenteric tissues by a mechanism dependent on NO. Specifically, pharmacological inhibitors of NO synthase remarkably abrogated the 15d-PGJ2-mediated suppression of neutrophil migration to the inflammatory site. Moreover, inducible NOS-/- mice were not susceptible to 15d-PGJ2-mediated suppression of neutrophil migration to the inflammatory sites when compared with their wild type. In addition, 15d-PGJ2-mediated suppression of neutrophil migration appeared to be independent of the production of cytokines and chemokines, since their production were not significantly affected in the carrageenan-injected peritoneal cavities. Finally, up-regulation of carrageenan-triggered ICAM-1 expression in the mesenteric microcirculation vessels was abrogated by pretreatment of wild-type mice with 15d-PGJ2, whereas 15d-PGJ2 inhibited F-actin rearrangement process in neutrophils. Taken together these findings demonstrated that 15d-PGJ2 suppresses inflammation-initiated neutrophil migration in a mechanism dependent on NO production in mesenteric tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Capillaries / metabolism
  • Carrageenan / pharmacology
  • Cell Adhesion
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukocyte Rolling*
  • Ligands
  • Male
  • Mesentery / blood supply
  • Mice
  • Mice, Knockout
  • Microcirculation
  • Neutrophils / drug effects
  • Neutrophils / immunology*
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • PPAR gamma / metabolism*
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / metabolism
  • Prostaglandin D2 / pharmacology


  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Actins
  • Ligands
  • PPAR gamma
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide
  • Carrageenan
  • Nitric Oxide Synthase Type II
  • Prostaglandin D2