Respective contribution of cytosolic phospholipase A2α and secreted phospholipase A₂ IIA to inflammation and eicosanoid production in arthritis.

Phospholipase A₂s (PLA₂) play a key role in generation of eicosanoids. Cytosolic PLA₂α (cPLA₂α) is constitutively expressed in most cells, whereas IIA secreted PLA₂ (sPLA₂-IIA) is induced during inflammation and is present at high levels in the synovial fluid of rheumatoid arthritis patients. In mice, both cPLA₂α and sPLA₂-IIA have been implicated in autoimmune arthritis; however, the respective contribution of these two enzymes to the pathogenesis and production of eicosanoids is unknown. We evaluated the respective role of cPLA₂α and sPLA₂-IIA with regard to arthritis and eicosanoid profile in an in vivo model of arthritis. While arthritis was most severe in mice expressing both enzymes, it was abolished when both cPLA₂α and sPLA₂-IIA were lacking. cPLA₂α played a dominant role in the severity of arthritis, although sPLA₂-IIA sufficed to significantly contribute to the disease. Several eicosanoids were modulated during the course of arthritis and numerous species involved sPLA₂-IIA expression. This study confirms the critical role of PLA₂s in arthritis and unveils the distinct contribution of cPLA₂α and sPLA₂-IIA to the eicosanoid profile in arthritis.

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