Lipid mediators in rheumatic diseases: novel means of regulation


Lipid mediators have an important role in the pathogenesis of rheumatic diseases, and enzymes and receptors involved in lipid mediator biosynthesis or action constitute valuable therapeutic targets. The overall aim of our research is to gain novel understanding of regulation of lipid mediators in rheumatoid arthritis (RA) and idiopathic inflammatory myopathies (IIM) to improve treatment of patients.

Microsomal prostaglandin E synthase (mPGES-1) is an attractive alternative target for anti-inflammatory treatment with improved selectivity and safety compared to NSAIDs. Our data suggest that the combination of anti-rheumatic treatments with selective inhibition of mPGES-1 would be beneficial for patients with RA and IIM. To assess the effects of selective inhibition of mPGES-1 on pathogenic mechanisms we perform studies in knock-out mice (mPGES1-/-) and pharmacological modulation of mPGES-1 activity. We aim to compare mechanisms affected by mPGES-1 inhibitors and COX inhibitors in vitro and in vivo models of inflammation and identify novel biomarkers and pathways related to anti-inflammatory or side effects of the drugs.

We have found that both COX- and 5-LO pathways are markedly up-regulated at sites of inflammation in IIM patients. Moreover, our preliminary results suggest a deregulation of lipid metabolism in this disease. We aim to study a role of lipid metabolism/mediators in the pathogenesis of IIM and determine novel biomarkers and potential therapeutic targets.