Blockade of Prostaglandin E2 Receptor 4 Ameliorates Nephrotoxic Serum Nephritis.

Blockade of Prostaglandin E2 Receptor 4 Ameliorates Nephrotoxic Serum Nephritis. Am J Physiol Renal Physiol. 2018 Oct 17;: Authors: Aringer I, Artinger K, Kirsch AH, Schabhüttl C, Jandl K, Bärnthaler T, Mooslechner A, Herzog SA, Uhlig M, Kirsch A, Frank S, Banas M, Pollheimer M, Eller P, Rosenkranz AR, Heinemann A, Eller K Abstract Prostaglandin E2 (PGE2) signaling is known to modulate inflammation and vascular resistance. Receptors of PGE2 (E-type prostanoid receptors, EP) might be an attractive pharmacological target in immune-mediated diseases such as glomerulonephritis. We hypothesized that selective EP4 antagonism improves nephrotoxic serum nephritis (NTS) by its anti-inflammatory properties. Mice were subjected to NTS and treated with the EP4 antagonist ONO AE3-208 [10 mg/kg bw/day] or vehicle starting from disease initiation. In one set of experiments treatment was started 4 days after NTS induction. Tubular epithelial cells were evaluated in vitro under starving conditions. EP4 antagonist treatment significantly improved the NTS phenotype without affecting blood pressure levels. Remarkably, the improved NTS phenotype was also observed when treatment was started 4 days after NTS induction. EP4 antagonism decreased tubular chemokine (C-x-c motif) ligand -1 ( Cxcl-1) and -5 ( Cxcl-5) expression and thereby subsequently reduced interstitial neutrophil infiltration into the kidney. In vitro, tubular epithelial cells increasingly...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research