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Peroxisome Proliferator‐Activated Receptor gamma (PPARgamma) ligand, 15d‐PGJ2, represses pro‐inflammatory responses in vascular endothelial cells: The role of nitric oxide
Author(s) -
Polikandriotis John A,
Hwang Jinah,
Rojas Mauricio,
Hart C Michael
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1165
Subject(s) - peroxisome proliferator activated receptor , nitric oxide , peroxisome proliferator activated receptor gamma , chemistry , peroxisome , microbiology and biotechnology , receptor , peroxisome proliferator activated receptor alpha , ligand (biochemistry) , cancer research , biology , nuclear receptor , biochemistry , transcription factor , gene , organic chemistry
Purpose PPARgamma activation prevents atherosclerotic vascular disease and reduces vascular dysfunction and inflammation in diabetic and non‐diabetic subjects. We have previously shown that PPARgamma ligands enhance endothelial nitric oxide (NO) bioavailability. We hypothesized PPARgamma‐induced increases in endothelial NO production contribute to previously described vascular anti‐inflammatory effects following PPARgamma activation. Methods Human umbilical vein endothelial cells (HUVEC) were treated with 15d‐PGJ2 with or without human recombinant TNFa (100U for 2 hours) followed by analysis of cytokine production, adhesion molecule expression, and monocyte adhesion. In separate studies, HUVEC were treated with the NOS inhibitor, L‐NAME, prior to treatment with PPARgamma ligands. Results 15d‐PGJ2 attenuated TNFa mediated induction of IL‐6, IL‐8, MCP‐1, and IP‐10, endothelial‐monocyte adhesion, and ICAM, VCAM, and E‐selectin expression. The NOS inhibitor, L‐NAME, reduced 15d‐PGJ2 mediated NO production and attenuated 15d‐PGJ2 repression of TNFa mediated ICAM expression. Conclusions These data indicate that treatment with 15d‐PGJ2 suppressed TNFa‐stimulated expression of inflammatory genes in vascular endothelial cells. L‐NAME‐mediated attenuation of the ability of 15d‐PGJ2 to suppress ICAM expression suggests that PPARgamma‐stimulated NO production may contribute to the anti‐inflammatory effects of PPARgamma ligands in vascular endothelial cells. This work is supported by grants from the Veterans Affairs Research Service