Transcription-based COX-2 inhibition: A therapeutic strategy

Kenneth K. Wu

doi:10.1160/TH06-07-0403

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(04): 417-422
DOI: 10.1160/TH06-07-0403

Theme Issue Article

Schattauer GmbH

Transcription-based COX-2 inhibition: A therapeutic strategy

Kenneth K. Wu

¹Vascular Biology Research Center and Division of Hematology, Department of Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA

› Author Affiliations

Abstract

Summary

Potent selective cyclooxygenase-2 (COX-2) inhibitors are effective in controlling inflammatory disorders but are associated with cardiovascular complications. Their clinical use has been severely limited. We propose that transcription-based inhibition of COX-2 expression represents a therapeutic strategy that may circumvent the undesired complications of COX-2 inhibitors. Reported data from several laboratories including ours have identified C/EBPβ as a key transactivator mediating COX-2 transcriptional activation induced by diverse pro-inflammatory mediators. Results from our recent work show that sodium salicylate at pharmacological concentrations inhibits C/EBPβ binding to COX-2 promoter by direct inhibition of p90 ribosomal S6 kinase (RSK). RSK phosphorylates C/EBPβ and stimulates its binding to enhancer elements. We propose that RSK1/2 is a potential target for screening drugs with novel anti-inflammatory and anti-neoplastic therapeutic potentials.

Keywords

Cyclooxygenase-2 - inflammation - C/EBPβ,aspirin - P90 ribosomal S6 kinase

Full Text

References

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