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Ligand specific Peroxisome Proliferator‐Activated Receptor gamma (PPARgamma) modulation of pro‐inflammatory responses
Author(s) -
Polikandriotis John A,
Hwang Jinah,
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-a
Subject(s) - peroxisome proliferator activated receptor , transcription factor , tumor necrosis factor alpha , microbiology and biotechnology , umbilical vein , chemistry , nuclear receptor , receptor , ligand (biochemistry) , reporter gene , cancer research , gene expression , biology , biochemistry , immunology , gene , in vitro
Purpose Previous studies have shown that PPARgamma ligands exhibit potent anti‐inflammatory properties. PPARgamma modulates transcriptional activity not only through its ability to act as a transcription factor but also through sequestration of cofactors required for gene induction at other promoter sites. We hypothesized that PPARgamma inhibits pro‐inflammatory gene expression through ligand‐specific regulation of cofactor complexes required for promoter activity. Methods Human umbilical vein endothelial cells (HUVEC) were treated with 15d‐PGJ2, ciglitizone, or rosiglitazone for 24 hours ± treatment with human recombinant TNFa. HUVEC were then collected for analysis of transcription factor activity and media were analyzed for IL‐6 production. Results Each PPARgamma ligand studied caused comparable activation of a HUVEC luciferase reporter gene. Despite comparable degrees of PPARgamma activation, each ligand attenuated TNFa mediated IL‐6 induction in a ligand specific manner and differentially regulated NFkB activity. Conclusions These data indicate that PPARgamma ligands differentially suppress TNFa‐mediated inflammatory effects in vascular endothelial cells and contribute to our understanding of the molecular mechanisms of PPARgamma mediated repression of inflammatory genes in the vasculature. This work is supported by grants from the Veterans Affairs Research Service