当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > Tobacco smoke affects expression of peroxisome proliferator-activated receptor-gamma in monocyte/macrophages of patients with coronary heart disease.

Tobacco smoke affects expression of peroxisome proliferator-activated receptor-gamma in monocyte/macrophages of patients with coronary heart disease.

Abstract：

BACKGROUND AND PURPOSE:Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator-activated receptor (PPAR)gamma activation reduces inflammation and atherosclerosis, expression of PPARgamma in cells and its modulation by smoking are poorly investigated. We previously reported that monocyte/macrophages from healthy smokers exhibited an enhanced constitutive expression of PPARgamma. Here, we evaluated PPARgamma expression and basal cytokine release in monocytes and monocyte-derived macrophages (MDMs) from 85 CHD patients, classified by their smoking habit (smokers, non-smokers and ex-smokers), and assessed the role of PPARgamma ligands in this context. EXPERIMENTAL APPROACH:PPARgamma protein was detected by Western blot and semi-quantified by PPARgamma/beta-actin ratio; cytokine release was measured by elisa and nuclear factor-kappaB (NF-kappaB) translocation by electrophoretic mobility shift assays. KEY RESULTS:As compared to the other groups, MDMs from smoker CHD patients exhibited a reduced PPARgamma/beta-actin ratio and an increased spontaneous release of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6, but with no major variations in monocytes. In cells from selected CHD patients, rosiglitazone inhibited TNF-alpha release and NF-kappaB translocation induced by phorbol-12-myristate 13-acetate. The selective PPARgamma antagonist GW9662 reversed these effects, with some variations related to smoking habit. CONCLUSIONS AND IMPLICATIONS:In CHD patients, exposure to tobacco smoke profoundly affected PPARgamma expression, and this was related to levels of secretion of pro-inflammatory cytokines. MDMs from CHD smokers showed the lowest PPARgamma expression and released more inflammatory cytokines. Moreover, rosiglitazone's ability to inhibit cytokine release and its reversal by GW9662 clearly indicated PPARgamma involvement in these changes in CHD patients.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Amoruso A,Gunella G,Rondano E,Bardelli C,Fresu LG,Ferrero V,Ribichini F,Vassanelli C,Brunelleschi S

doi

10.1111/j.1476-5381.2009.00442.x

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

1276-84

issue

eissn

0007-1188

issn

1476-5381

pii

BPH442

journal_volume

158

pub_type

杂志文章

在线工具

Tobacco smoke affects expression of peroxisome proliferator-activated receptor-gamma in monocyte/macrophages of patients with coronary heart disease.