Article Text

PDF
SP0060 Potential New Strategies for Inhibiting Prostaglandins
  1. P.-J. Jakobsson
  1. Department of Medicine, Karolinska Institutet, Stockholm, Sweden

Abstract

Microsomal prostaglandin E synthase-1 (mPGES-1) constitutes a drug target for inflammation, fever and pain. mPGES-1 catalyzes the biosynthesis of prostaglandin (PG) E2 from cyclooxygenase (Cox) -derived PGH2, which in turn is derived from arachidonic acid. mPGES-1 is mainly associated with inflammation and it is known to be up regulated by various pro-inflammatory cytokines like IL-1 beta and TNF-alpha. Mice devoid of mPGES-1 activity display resistance to development of experimental arthritis, fever, pain, symptoms following stroke, atherosclerosis and breathing anomalies induced by hypoxia. Conversely, the enzyme seems to have a protective role in wound healing and remodeling following myocardial infarction. Inhibitors of mPGES-1 have been developed by several groups. However, their characterization in animal models of inflammation, or other models previously used to study mPGES-1 knock-out mice, remains limited. One reason is the fact that a majority of the potent inhibitors of human mPGES-1 are significantly less potent or even completely inactive towards rodent mPGES-1. In addition, the impact of mPGES-1 inhibitors on the prostaglandin profile should be further investigated in various cells and in vivo systems, as their effects but also side-effects will largely depend on the particular prostaglandin profile they elicit. In this presentation, an update will be provided on the characterization of mPGES-1 inhibitors by us and others.

Disclosure of Interest P.-J. Jakobsson Consultant for: NovaSAID AB

DOI 10.1136/annrheumdis-2014-eular.6215

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.