Leptin potentiates IFN-γ-induced expression of nitric oxide synthase and cyclo-oxygenase-2 in murine macrophage J774A.1

1 Leptin, a pleiotropic hormone believed to regulate body weight, has recently been associated with inflammatory states and immune activity. Here we have studied the effect of leptin on expression of IFN-gamma-induced nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2), both prominent markers of macrophage activation, using the murine macrophage J774A.1 cell line. 2 After 24 h of incubation, leptin (1-10 mug ml(-1)) potently synergized with IFN-gamma (100 U ml(-1)) in nitric oxide (NO) release, evaluated as nitrite and nitrate (NOx), and prostaglandin E-2 (PGE(2)) production in culture medium. 3 The observed increase of NO and PGE(2) was related to enhanced expression of the respective inducible enzyme isoforms, measured in mRNA and protein by RT-PCR and Western blot analysis, respectively. 4 When cells were stimulated only with leptin, a weak induction of NO and PGE(2) release and of the expression of related inducible enzymes was observed. 5 Moreover IFN-gamma increased the expression of the functional form of leptin receptor (Ob-Rb) and this effect was potentiated by leptin in a concentration-dependent manner. 6 These data suggest that macrophages, among the peripheral immune cells, represent a target for leptin and confirm the relevance of this hormone in the pathophysiology of inflammation.