CROSS TALK BETWEEN CPLA2, SPLA2S AND COXS IN KIDNEY CELL

炎症过程通常伴随着细胞因子的重新合成和细胞外释放。促炎细胞因子参与调节不同形式的磷脂酶A2 （PLA2）和环氧合酶的活性，这些酶在促炎类二十烷的释放中起重要作用。PLA2通过控制花生四烯酸（AA）的流动来调节生物活性类二十烷酸的产生。类二十烷酸与肾脏的许多炎症过程有关，包括与肾小球肾炎和小管间质疾病相关的炎症过程。各种PLA2S的生理和病理生理作用仍有待确定。肾小球系膜有助于肾小球的炎症状态。由于在我们的实验室中产生了cPLA2-/-小鼠，现在有可能了解PLA2在系膜细胞中产生类二十烷的独特作用。本应用中提出的研究将为各种肾小球病理生理过程的机制提供重要的新见解。更好地了解花生四烯酸释放和前列腺素产生的控制机制可能导致更有效地控制炎症过程。这可以导致独特的治疗干预措施，以减少各种肾脏疾病的发病率和死亡率。

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.