Cytosolic Phospholipase A2 Regulates TNF-Induced Production of Joint Destructive Effectors in Synoviocytes

• DOI: 10.1371/journal.pone.0083555
• Publication Date: 2013-12-13T01:15:23Z
• Authors: Randi M. Sommerfelt; Astrid J. Feuerherm; Kymry Jones; Berit Johansen
• Keywords: Proinflammatory cytokine; Interleukin 8

IntroductionRheumatoid arthritis (RA) is an inflammatory disease of the joint characterized by chronic synovitis causing pain, swelling and loss function due to destruction cartilage bone. The complex series pathological events occurring in RA largely regulated via excessive production pro-inflammatory cytokines, most prominent being tumor necrosis factor (TNF). objective this work was elucidate possible involvement group IVA cytosolic phospholipase A2 (cPLA2α) TNF-induced regulation destructive effectors RA, evaluate potential cPLA2α as a future therapeutic target. MethodsThe (TNF)-induced intracellular signaling cascades synoviocytes (synovial fibroblast-like cells) analyzed arachidonic acid (AA) release assay, synoviocyte enzyme activity gene expression analysis real-time PCR ELISA immunoassay for detection prostaglandin E2 (PGE2), interleukin 8 (IL8) stromelysin-1 (MMP3), respectively. ResultsInhibitors (AVX002, ATK) significantly reduced cellular AA, PGE2, IL8 MMP3. This reduction evident both at transcriptional, protein or metabolite levels. Interestingly, inhibition affected several key points arachidonyl cascade; AA-release, cyclooxygenase-2 (COX2) PGE2 production. Furthermore, results suggest that subject transcriptional auto-regulation resulted PLA2G4A TNF-stimulated synoviocytes. ConclusionscPLA2α appears be important regulator central inflammation destruction, namely MMP3, IL8, COX2, PGE2. Decreased transcription COX2 genes response further self-reinforcing effect TNF. Collectively, these support attractive target candidate its reduces multiple factors involved pathogenesis.