The renal medullary thick ascending limb as a model for understanding lipid mediators in sepsis

Cytokines are an essential component in those mechanisms that depress renal function in response to inflammatory diseases of the kidney. We have addressed the role of tumor necrosis factor (TNF) in mediating changes in renal function by isolating a nephron segment, the medullary thick ascending limb of Henle's loop (mTAL), and studying the effects of TNF on ion transport via changes in the activity of two epoxygenases, cyclooxygenase (COX) and cytochrome P450 (CYP450) monooxygenase. This nephron segment generates 20-hydroxyeicosatetraenoic acid (20-HETE) as a principal arachidonate metabolite. However, when challenged with lipopolysaccharide (LPS), the mTAL expresses a considerable capacity to metabolize arachidonic acid (AA) via a COX pathway to form PGE2.