New insights into eicosanoid biosynthetic pathways: implications for arthritis

Abstract

Eicosanoid is a collective term for the family of lipid mediators derived from arachidonic acid (AA) metabolism. This complex family of lipids is comprised of prostaglandins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins (LXs). The most studied enzymatic pathway for AA metabolism proceeds via cyclooxygenase (COX). However, AA can also be metabolized by the lipoxygenases (LOXs) to LTs and HETEs, and recent studies have demonstrated a unique AA metabolic pathway mediated by both COX and LOX. Eicosanoids are also implicated as important mediators of several chronic inflammatory diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). Current therapies to treat RA and OA symptoms are directed toward the inhibition of enzymes and mediators generated within the eicosanoid pathway. This review will give insights into the current understanding of the eicosanoid biosynthetic pathway and its role in the RA and OA disease states. In addition, current therapies and future therapeutic targets within the eicosanoid pathway for the treatment of RA and OA will be discussed.

Keywords::

• cyclooxygenase
• eicosanoid
• inflammation
• leukotriene
• lipoxin
• lipoxygenase
• non-steroidal anti-inflammatory drugs
• osteoarthritis
• prostaglandin E synthase
• rheumatoid arthritis

Acknowledgements

The authors would like to thank Lihua Yang for her assistance. Kojima F and Kapoor M have contributed equally as first authors.