On interaction of activated protein C with human aortic smooth muscle cells attenuating the secretory group IIA phospholipase A2 expression
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Introduction: Pharmacological restriction of secretory group IIA phospholipase A2 (sPLA2-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 sPLA2-IIA expression, phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, and on DNA-binding activities of nuclear factor-κB (NF-κB) and CCAAT box enhancer binding protein-β (C/EBP-β) in human aortic smooth muscle cells (HASMC). Materials and methods: To achieve elevated sPLA2-IIA production as occurring during inflammation, HASMC were stimulated with interferon-γ (IFN-γ) alone and in combination with other inductors, thus modeling the strong sPLA2-IIA elevation by inflammation. Results and conclusions: APC inhibited the stimulated expression of sPLA2-IIA in HASMC dose-dependently (1-300 nM). At the same time, APC increased the phosphorylation of ERK 1/2 and decreased NF-κB and C/EBP-β 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 sPLA2-IIA inhibition. The obtained results show that APC effectively suppresses the up-regulated sPLA2-IIA expression, which might contribute to the reported beneficial effects of APC in the treatment of severe inflammatory disorders.
Details
Original language | English |
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Pages (from-to) | 69-76 |
Number of pages | 8 |
Journal | Thrombosis research |
Volume | 122 |
Issue number | 1 |
Publication status | Published - 2008 |
Peer-reviewed | Yes |
External IDs
PubMed | 17936881 |
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Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- Activated protein C, Endothelial protein C receptor, Protease-activated receptors, Secretory phospholipase A