The inflammatory process is generally accompanied by de novo synthesis and extracellular release of cytokines. Proinflammatory cytokines have been implicated in the modulation of activities of different forms of phospholipases A2 (PLA2) and cyclooxygenases which play important roles in release of proinflammatory eicosanoids. PLA2 regulate the production of bioactive eicosanoids by controlling the flow of arachidonic acid (AA). Eicosanoids have been implicated in many inflammatory processes in the kidney including those associated with glomerulonephritis and tubular interstitial diseases. The physiological and pathophysiological roles of the various PLA2S remain to be determined. The glomerular mesangium contributes to the inflammatory state of the glomerulus. Understanding distinct roles of the PLA2 in the generation of eicosanoids in mesangial cells is now possible because of the generation of cPLA2-/- mice in our laboratory. The studies proposed in this application will provide important new insights regarding the mechanisms responsible for various glomerular pathophysiological processes. The better understanding of control mechanisms responsible for arachidonic acid release and prostaglandin production may lead to more efficient manipulation of inflammatory process. This can lead to unique therapeutic interventions to reduce morbidity and mortality in various renal diseases.

F32DK010036

2000-09-01

1900-01-01