High Sodium Diet Activated NFκB Signaling Plays an Important Role in Renal Medullary COX2 Induction

Abstract

Renal medullary COX2 plays an important role in renal response to dietary sodium. NFκB is known as an important mediator of COX2 induction. The present study examined the role of NFκB in renal medullary COX2 induction following increased dietary sodium. High sodium diet (8% NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6J mice. Co‐immunofluorescence using a COX2 antibody and antibodies against AQP1, ClC‐K, AQP2 and CD31 showed that dietary sodium induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a 7±2 fold (P<0.05) increase of luciferase activity in renal medulla of the NFκB‐luciferase reporter mice following high sodium diet, and a robust induction of EGFP expression mainly localized in renal medullary interstitial cells of the NFκB‐EGFP reporter mice following high sodium diet. Treating C57Bl/6J mice with selective IκB kinase inhibitor IMD‐0354 (8mg/kg bw) substantially attenuated COX2 induction in renal medulla, and also significantly reduced urinary PGE2 following high sodium diet (from 1798±578 to 809±267 μg/24h, P<0.05). These data suggest a critical role of renal medullary NFκB signaling in the renal response to increased dietary sodium, which may account for the altered sodium balance observed in patients taking NFκB‐inhibiting drugs, such as Bortezomib. Research supported by NIH.