Protease-Activated Receptors Upregulate Cyclooxygenase-2 Expression in Human Endothelial Cells

Rebecca A. Houliston; Rosemary J. Keogh; David Sugden; Jayesh Dudhia; Tom D. Carter; Caroline P. D. Wheeler-Jones

doi:10.1055/s-0037-1613205

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 88(02): 321-328
DOI: 10.1055/s-0037-1613205

In Focus

Schattauer GmbH

Protease-Activated Receptors Upregulate Cyclooxygenase-2 Expression in Human Endothelial Cells

Rebecca A. Houliston

¹Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, Royal College Street, London

,

Rosemary J. Keogh

¹Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, Royal College Street, London

,

David Sugden

²Guy’s King’s and St. Thomas’ School of Biomedical Sciences, New Hunt’s House, London Bridge, London

,

Jayesh Dudhia

¹Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, Royal College Street, London

,

Tom D. Carter

³Department of Pharmacology, University College London, Gower Street, London, UK

,

Caroline P. D. Wheeler-Jones

¹Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, Royal College Street, London

› Author Affiliations

Abstract

Summary

We have previously shown that the serine protease thrombin and other G protein-coupled agonists acutely enhance synthesis and release of prostacyclin from human umbilical vein endothelial cells (HUVEC) through activation of cPLA₂α. Here, we show that thrombin and other physiological endothelial cell agonists upregulate COX-2 induction in HUVEC. Thrombin treatment caused a rapid and sustained increase in prostacyclin (PGI₂) synthesis from HUVEC. Thrombin and a selective protease-activated receptor-1 (PAR-1) peptide (TRAP) evoked doseand time-dependent increases in COX-2 protein expression which were equivalent to that induced by the proinflammatory cytokine IL-1α. Quantitative and real-time PCR analysis showed enhanced COX-2 mRNA expression in thrombinor TRAP-stimulated HUVEC whereas COX-1 expression was unaffected. A PAR-2 agonist peptide also induced COX-2 protein and mRNA expression with kinetics distinct from those of thrombin, and promoted PGI₂ release. These results demonstrate that regulation of COX-2 induction is an important functional response of HUVEC to PAR activation and suggest that PARs promote sustained upregulation of prostanoid production in human endothelium.

Keywords

Human endothelium - thrombin - cyclooxygenase - prostacyclin - protease-activated receptors

Full Text

References

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