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PMID: 16267130 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The antiinflammatory effect of laminar flow: the role of PPARgamma, epoxyeicosatrienoic acids, and soluble epoxide hydrolase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 46 ·2005-11-15 ·Pages 16747-52

Liu Y, Zhang Y, Schmelzer K, Lee TS, Fang X, Zhu Y, Spector AA, Gill S, Morisseau C, Hammock BD, Shyy JY

Abstract

We previously reported that laminar flow activates peroxisome proliferator-activated receptor gamma (PPARgamma) in vascular endothelial cells in a ligand-dependent manner that involves phospholipase A2 and cytochrome P450 epoxygenases. In this study, we investigated whether epoxyeicosatrienoic acids (EETs), the catalytic products of cytochrome P450 epoxygenases, are PPARgamma ligands. Competition and direct binding assays revealed that EETs bind to the ligand-binding domain of PPARgamma with K(d) in the microM range. In the presence of adamantyl-ureido-dodecanoic acid (AUDA), a soluble epoxide hydrolase (sEH)-specific inhibitor, EETs increased PPARgamma transcription activity in endothelial cells and 3T3-L1 preadipocytes. Inclusion of AUDA in the perfusing media enhanced, but overexpression of sEH reduced, the laminar flow-induced PPARgamma activity. Furthermore, laminar flow augmented cellular levels of EETs but decreased sEH at the levels of mRNA, protein, and activity. Blocking PPARgamma by GW9662 abolished the EET/AUDA-mediated antiinflammatory effect, which indicates that PPARgamma is an effector of EETs.

MeSH Terms
3T3-L1 Cells Animals Base Sequence Catalysis Cattle Cells, Cultured DNA Primers Down-Regulation Eicosanoids/physiology Epoxide Hydrolases/physiology Inflammation/physiopathology Mice PPAR gamma/physiology Reverse Transcriptase Polymerase Chain Reaction Solubility
Chemicals
DNA Primers Eicosanoids PPAR gamma Epoxide Hydrolases
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Liu Yi
Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA.
Zhang Yingjia
Schmelzer Kara
Lee Tzong-Shyuan
Fang Xiang
Zhu Yi
Spector Arthur A
Gill Sarjeet
Morisseau Christophe
Hammock Bruce D
Shyy John Y-J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0508081102
Published
2005-11-15
Epub
2005-00-02
Pages
16747-52
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1276614
Subset
IM
Grants
NHLBI NIH HHS · HL77448 · United States
NIEHS NIH HHS · F32 ES005707 · United States
NIEHS NIH HHS · ES02710 · United States
NHLBI NIH HHS · R01 HL072845 · United States
NIEHS NIH HHS · R01 ES002710 · United States
NIEHS NIH HHS · P30 ES005707 · United States
NIEHS NIH HHS · P42 ES004699 · United States
NIEHS NIH HHS · ES05707 · United States
NHLBI NIH HHS · R01 HL077448 · United States
NIEHS NIH HHS · ES04699 · United States
NHLBI NIH HHS · HL72845 · United States
NIEHS NIH HHS · R37 ES002710 · United States
External Links
PubMed source DOI: 10.1073/pnas.0508081102 PMC Full Text View journal details
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