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Leptin potentiates IFN‐γ‐induced expression of nitric oxide synthase and cyclo‐oxygenase‐2 in murine macrophage J774A.1
Author(s) -
Raso Giuseppina Mattace,
Pacilio Maria,
Esposito Emanuela,
Coppola Anna,
Di Carlo Raffaele,
Meli Rosaria
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704903
Subject(s) - leptin , nitric oxide synthase , nitric oxide , medicine , endocrinology , western blot , chemistry , macrophage , immune system , inflammation , leptin receptor , biology , immunology , biochemistry , in vitro , obesity , gene
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‐γ‐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. After 24 h of incubation, leptin (1–10 μg ml −1 ) potently synergized with IFN‐γ (100 U ml −1 ) in nitric oxide (NO) release, evaluated as nitrite and nitrate (NO x ), and prostaglandin E 2 (PGE 2 ) production in culture medium. 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. 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. Moreover IFN‐γ increased the expression of the functional form of leptin receptor (Ob‐Rb) and this effect was potentiated by leptin in a concentration‐dependent manner. 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.British Journal of Pharmacology (2002) 137 , 799–804. doi: 10.1038/sj.bjp.0704903