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

Abstract Phospholipase A 2 s (PLA 2 ) play a key role in generation of eicosanoids. Cytosolic PLA 2 α (cPLA 2 α) is constitutively expressed in most cells, whereas IIA secreted PLA 2 (sPLA 2 -IIA) is induced during inflammation and is present at high levels in the synovial fluid of rheumatoid arthritis patients. In mice, both cPLA 2 α and sPLA 2 -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 cPLA 2 α and sPLA 2 -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 cPLA 2 α and sPLA 2 -IIA were lacking. cPLA 2 α played a dominant role in the severity of arthritis, although sPLA 2 -IIA sufficed to significantly contribute to the disease. Several eicosanoids were modulated during the course of arthritis and numerous species involved sPLA 2 -IIA expression. This study confirms the critical role of PLA 2 s in arthritis and unveils the distinct contribution of cPLA 2 α and sPLA 2 -IIA to the eicosanoid profile in arthritis.