Prostaglandin E synthase in the pathophysiology of arthritis

Prostaglandin E synthase (PGES) is a recently identified terminal enzyme that acts downstream of cyclooxygenase and catalyzes the conversion of prostaglandin (PG) H2 to PGE2. At least three isozymes have been cloned so far, which are called membrane-associated PGES (mPGES)-1, mPGES-2, and cytosolic PGES. Among them, mPGES-1 is induced by various inflammatory stimuli in some cells and tissues. Induction of mPGES-1 in the component of articular tissues of patients with rheumatoid arthritis and osteoarthritis has been demonstrated in vitro. Recent studies using adjuvant induced arthritis model have shown the increase of mPGES-1 expression resulted in the increase of PGE2 production at the sites of inflammation. In addition, reports of mPGES-1-deficient mice clearly suggest the role of mPGES-1 in the process of chronic inflammation such as collagen-induced arthritis and collagen antibody induced arthritis in vivo. Thus, recent in vitro and in vivo findings suggest that mPGES-1 may be a novel therapeutic target for arthritis. This paper introduces recent advances in research about the role of PGES in the pathophysiology of arthritis.