title: Phospholipase A2 and arthritis.
abstract: Over the last 30 years, interest in PLA2 has grown beyond its enzymatic capacity to cleave phospholipids. It has been recognized as the rate-limiting step in the release of arachidonic acid and subsequent formation of prostaglandins, leukotrienes, and other bioactive lipids. Subsequently, PLA2 has not only been found to be present in high concentrations in inflammatory arthritis, but also to induce inflammation when injected into animals. At the same time, investigators into mechanisms of signal transduction demonstrated that a variety of cytokines including IL-1 and TNF, which are found in high concentrations in synovial fluid from patients with RA, stimulate PLA2 activity. These investigations demonstrated further the central role for PLA2 in inflammatory events, especially inflammatory arthritis. Numerous other PLA2 proteins, in addition to the low molecular weight synovial fluid/platelet enzyme, also have been characterized. Their clinical role in arthritis is yet to be elucidated. Human proteins which either inhibit or stimulate PLA2 have also been identified, characterized, and cloned. More recently, exciting investigations, primarily from biotechnology and pharmaceutical companies, into inhibitors of PLA2 have been reported. New PLA2-regulating compounds, which will hopefully move from the laboratory and through clinical trials and then be used to treat patients with arthritis, are on the horizon.
authors.affiliation: Department of Medicine, Medical College of Pennsylvania, Philadelphia.
authors.forename: J S
authors.initials: JS
authors.lastname: Bomalaski
authors.forename: M A
authors.initials: MA
authors.lastname: Clark
mesh_terms: D001168:Arthritis / Q000201:enzymology*; D006801:Humans; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2
chemical_list: D010741:Phospholipases A; D054467:Phospholipases A2