Aringer, Ida and Artinger, Katharina and Kirsch, Alexander H. and Schabhuettl, Corinna and Jandl, Katharina and Baernthaler, Thomas and Mooslechner, Agnes A. and Herzog, Sereina A. and Uhlig, Moritz and Kirsch, Andrijana and Frank, Sasa and Banas, Miriam and Pollheimer, Marion and Eller, Philipp and Rosenkranz, Alexander R. and Heinemann, Akos and Eller, Kathrin (2018) Blockade of prostaglandin E-2 receptor 4 ameliorates nephrotoxic serum nephritis. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 315 (6). F1869-F1880. ISSN 1931-857X, 1522-1466
Full text not available from this repository. (Request a copy)Abstract
Prostaglandin E-2 (PGE(2)) signaling is known to modulate inflammation and vascular resistance. Receptors of PGE(2) [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 body wt(-1).day(-1)] 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 (Cxcl) 1 and Cxcl-5 expression and thereby subsequently reduced interstitial neutrophil infiltration into the kidney. In vitro, tubular epithelial cells increasingly express Cxcl-5 mRNA and Cxcl-5 protein when treated with PGE(2) or an EP4 agonist under starving conditions, which is blunted by EP4 antagonist treatment. Together, EP4 antagonism improves the NTS phenotype probably by decreasing mainly Cxcl-5 production in tubular cells thereby reducing renal neutrophil infiltration.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T-CELLS; KIDNEY-DISEASE; (PRO)RENIN RECEPTOR; EP4 RECEPTOR; SYSTEM; PGE(2); GLOMERULONEPHRITIS; LOCALIZATION; STIMULATION; INVOLVEMENT; glomerulonephritis; immune cells; prostanoids; tubular cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Oct 2019 08:42 |
| Last Modified: | 04 Oct 2019 08:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13409 |
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