Display Settings:

Format

Send to:

Choose Destination
Thromb Res. 2008;122(1):69-76. Epub 2007 Oct 22.

On interaction of activated protein C with human aortic smooth muscle cells attenuating the secretory group IIA phospholipase A2 expression.

Author information

  • 1Institute of Clinical Chemistry and Laboratory Medicine, Technical University of Dresden, Medical Faculty Carl Gustav Carus, Dresden, Germany. menschik@rcs1.urz.tu-dresden.de

Abstract

INTRODUCTION:

Pharmacological restriction of secretory group IIA phospholipase A(2) (sPLA(2)-IIA) expression is thought to be beneficial in the treatment of inflammatory diseases such as sepsis and septic shock. In this study we investigated the effects of activated protein C (APC) on sPLA(2)-IIA expression, phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, and on DNA-binding activities of nuclear factor-kappaB (NF-kappaB) and CCAAT box enhancer binding protein-beta (C/EBP-beta) in human aortic smooth muscle cells (HASMC).

MATERIALS AND METHODS:

To achieve elevated sPLA(2)-IIA production as occurring during inflammation, HASMC were stimulated with interferon-gamma (IFN-gamma) alone and in combination with other inductors, thus modeling the strong sPLA(2)-IIA elevation by inflammation.

RESULTS AND CONCLUSIONS:

APC inhibited the stimulated expression of sPLA(2)-IIA in HASMC dose-dependently (1-300 nM). At the same time, APC increased the phosphorylation of ERK 1/2 and decreased NF-kappaB and C/EBP-beta DNA-binding activities in these cells, as compared with respective stimulated controls. Reverse transcriptase-polymerase chain reaction and cell-based ELISA reveal an endothelial protein C receptor (EPCR) expression in HASMC. Application of antibodies against EPCR and protease-activated receptor-1 (PAR-1) reduced the APC-induced ERK 1/2 activation and the treatment of cells with a PAR-1 antagonist diminished the sPLA(2)-IIA inhibition. The obtained results show that APC effectively suppresses the up-regulated sPLA(2)-IIA expression, which might contribute to the reported beneficial effects of APC in the treatment of severe inflammatory disorders.

PMID:
17936881
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk