TY - JOUR T1 - Expression and regulation of microsomal prostaglandin E synthase-1 in human osteoarthritic cartilage and chondrocytes. JF - The Journal of Rheumatology JO - J Rheumatol SP - 887 LP - 895 VL - 32 IS - 5 AU - Xinfang Li AU - Hassan Afif AU - Saranette Cheng AU - Johanne Martel-Pelletier AU - Jean-Pierre Pelletier AU - Pierre Ranger AU - Hassan Fahmi Y1 - 2005/05/01 UR - http://www.jrheum.org/content/32/5/887.abstract N2 - OBJECTIVE: Elevated production of prostaglandin E2 (PGE2) plays an important role in the pathogenesis of arthritis. Recently, an inducible microsomal prostaglandin E synthase-1 (mPGES-1) was identified. This enzyme is functionally coupled with cyclooxygenase-2 (COX-2) and converts the COX product PGH2 to PGE2. We analyzed expression of mPGES-1 in human normal and osteoarthritic (OA) cartilage and determined the effect of different inflammatory agonists on the expression of mPGES-1 in OA chondrocytes. METHODS: Expression of mPGES-1 mRNA and protein in cartilage was determined by quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. OA chondrocytes were treated with different inflammatory agents, and mPGES-1 protein expression was evaluated by Western blot. Activation of the mPGES-1 promoter was assessed in transient transfection experiments. RESULTS: Levels of mPGES-1 mRNA and protein were markedly elevated in OA versus normal cartilage. Treatment of chondrocytes with interleukin 1beta (IL-1beta) induced expression of mPGES-1 protein in a dose- and time-dependent manner. This appears to occur at the transcriptional level, as IL-1beta induced expression of mPGES-1 mRNA and the activity of this gene promoter. Tumor necrosis factor-alpha (TNF-alpha) and IL-17 also upregulated expression of mPGES-1 protein and displayed a synergistic effect with IL-1beta. Peroxisome proliferator-activated receptor-gamma ligands, 15-deoxy-delta(12,14)-prostaglandin J2 and troglitazone, inhibited IL-1beta-induced mPGES-1 protein expression, an effect that was reversed by exogenous PGE2. CONCLUSION: Our study shows that mPGES-1 expression is upregulated in OA versus normal cartilage and that proinflammatory cytokines increased mPGES-1 expression in chondrocytes. These data suggest that mPGES-1 may prove to be an interesting therapeutic target for controlling PGE2 synthesis. ER -