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20-Hydroxyeicosatetraenoic acid inhibits ATP-induced COX-2 expression via peroxisome proliferator activator receptor-? in vascular smooth muscle cells.

ABSTRACT:

Background and purpose

20-Hydroxyeicosatetraenoic acid (20-HETE), formed from arachidonate by cytochrome P450, regulates vascular smooth muscle cell (VSMC) function. Because 20-HETE may activate peroxisome proliferator activator receptors (PPARs) and may participate in inflammatory responses, we asked whether 20-HETE may inhibit cyclooxygenase 2 (COX-2) expression by activating PPARs in VSMC.

Experimental approach

Quiescent neonatal VSMC (R22D cell line), were incubated with 20-HETE, synthetic ligands of PPARs, or inhibitors of the extracellular signal regulated kinase (ERK1/2), c-jun N-terminal kinase and the transcription factor activated protein-1 before adding ATP?S. mRNA and protein expression of COX-2 and the promoter luciferase activity of COX-2 and PPAR response element were determined.

Key results

Pretreatment with 20-HETE (5-10 µM) significantly inhibited ATP?S-induced COX-2 mRNA and protein expression in VSMC. The inhibitory effect of 20-HETE on COX-2 expression was mimicked by WY14643, a PPAR? ligand and inhibited by MK886, a PPAR? inhibitor or by transfection of shRNA for PPAR?. Both 20-HETE and WY14643 significantly increased the PPAR-response element luciferase activity. Furthermore, ATP?S-induced activation of the COX-2 promoter containing the activated protein-1 site was also inhibited by pretreatment with 20-HETE, which was reversed by MK886 or by transfection with shRNA for PPAR?.

Conclusions and implications

The PPAR? may mediate the inhibitory effects of 20-HETE on COX-2 expression through a negative cross-talk between PPAR? and the COX-2 promoter.

SUBMITTER: Liang CJ

PROVIDER: S-EPMC3111683 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Publications

20-Hydroxyeicosatetraenoic acid inhibits ATP-induced COX-2 expression via peroxisome proliferator activator receptor-α in vascular smooth muscle cells.

Liang Chan-Jung CJ Tseng Ching-Ping CP Yang Chuen-Mao CM Ma Yunn-Hwa YH

British journal of pharmacology 20110601 4

<h4>Background and purpose</h4>20-Hydroxyeicosatetraenoic acid (20-HETE), formed from arachidonate by cytochrome P450, regulates vascular smooth muscle cell (VSMC) function. Because 20-HETE may activate peroxisome proliferator activator receptors (PPARs) and may participate in inflammatory responses, we asked whether 20-HETE may inhibit cyclooxygenase 2 (COX-2) expression by activating PPARs in VSMC.<h4>Experimental approach</h4>Quiescent neonatal VSMC (R22D cell line), were incubated with 20-HE ...[more]

PMID: 21323895

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