Ciglitazone inhibits plasmin-induced proinflammatory monocyte activation via modulation of p38 MAP kinase activity.

Abstract:

:Plasmin triggers chemotaxis and NF-kappa B- and AP-1-mediated proinflammatory gene expression in human peripheral monocytes (PM). Compared with macrophages and dendritic cells, PM express mainly the peroxisome proliferator-activated receptor (PPAR) gamma and traces of PPAR alpha as detected by semiquantitative RT-PCR and immunoblotting. The PPAR gamma agonist ciglitazone, but not the PPAR alpha agonist clofibric acid, concentration-dependently inhibited the plasmin-, but not the FMLP-induced PM chemotaxis. Similarly, release of interleukin (IL)-1 alpha, IL-1 beta and tumor necrosis factor (TNF)-alpha from plasmin-stimulated PM was concentration-dependently inhibited by ciglitazone, but not by clofibric acid, while the LPS-induced TNF-alpha release remained unaffected by any of both PPAR agonists. Ciglitazone activates PPAR gamma as shown by a novel surface plasmon resonance analysis and inhibits the plasmin-induced activation of NF-kappa B and AP-1. It also inhibits p38 MAPK phosphorylation essential for the plasmin-induced PM chemotaxis and gene activation. Thus, activation of PPAR gamma by ciglitazone may allow controLling of the plasmin-mediated recruitment and activation of PM at sites of inflammation.

journal_name

Thromb Haemost

authors

Syrovets T,Schüle A,Jendrach M,Büchele B,Simmet T

keywords:

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

274-81

issue

2

eissn

0340-6245

issn

2567-689X

journal_volume

88

pub_type

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