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Multiple phospholipase A2 enzymes participate in the inflammatory process in osteoarthritic cartilage

Objective: The aim of this study was to determine the involvement of pro-inflammatory phospholipase A2 (PLA2) enzymes in human chondrocytes from patients with osteoarthritis (OA). Methods: PLA2 involvement in OA chondrocytes was analysed by (a) arachidonic acid (AA) and oleic acid release, (b) PLA2 mRNA analysis, and (c) prostaglandin E2 (PGE2) production in cultured OA chondrocytes in response to various cytokines and platelet activating factor (PAF). Results: Pro-inflammatory cytokines and PAF stimulation led to increased AA release, interleukin (IL)-1β and tumour necrosis factor (TNF) being the strongest inducers. The pattern of oleic acid release was similar to but less prominent than AA release, suggesting that predominantly arachidonyl selective enzymes were activated. IL-1β, TNF, IL-6, and IL-8 upregulated secretory group IIA, IID, and V phospholipase A2 (sPLA2-IIA, -IID, -V) and cytosolic group IVA phospholipase A2 (cPLA2-IVA) expression, where induction of chondrocyte sPLA2-IID is a novel finding. Furthermore, IL-1β, TNF, and IL-6 also induced COX2 expression. PAF induced expression of group IIA, IID and IVA PLA2, and COX2. In line with its anti-inflammatory properties, IL-4 was unable to induce either AA release or expression of PLA2s or COX2. IL-1β and TNF strongly increased PGE2 production, with IL-1β as the most prominent inducer. Conclusion: Multiple PLA2 isoforms are expressed and influenced by pro-inflammatory stimuli in OA chondrocytes. Hence, several PLA2 enzymes may contribute to chondrocyte function by their upregulation and activation, and increased AA release and PGE2 production may therefore be important effectors in OA pathophysiology. PLA2 enzymes and cPLA2-IVA in particular are thus possible therapeutic targets in OA.