Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Aringer, I; Artinger, K; Kirsch, AH; Schabhüttl, C; Jandl, K; Bärnthaler, T; Mooslechner, AA; Herzog, SA; Uhlig, M; Kirsch, A; Frank, S; Banas, M; Pollheimer, M; Eller, P; Rosenkranz, AR; Heinemann, A; Eller, K.
Blockade of prostaglandin E₂ receptor 4 ameliorates nephrotoxic serum nephritis.
Am J Physiol Renal Physiol. 2018; 315(6):F1869-F1880 Doi: 10.1152/ajprenal.00113.2018 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz: Aringer Ida; Eller Kathrin
Co-Autor*innen der Med Uni Graz: Artinger Katharina; Bärnthaler Thomas; Eller Philipp; Frank Sasa; Heinemann Akos; Herzog Sereina Annik; Jandl Katharina; Kirsch Alexander; Kirsch Andrijana; Mooslechner Agnes Anna; Pollheimer Marion; Rosenkranz Alexander; Schabhüttl Corinna
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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 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 expressed Cxcl-5 mRNA and Cxcl-5 protein when treated with PGE₂ or an EP4 agonist under starving conditions, which was 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.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Anti-Inflammatory Agents - pharmacology; Cell Line -; Chemokine CXCL1 - genetics; Chemokine CXCL1 - metabolism; Chemokine CXCL5 - genetics; Chemokine CXCL5 - metabolism; Disease Models, Animal -; Down-Regulation -; Glomerulonephritis - blood; Glomerulonephritis - immunology; Glomerulonephritis - prevention & control; Interleukin-6 - genetics; Interleukin-6 - metabolism; Kidney Tubules - drug effects; Kidney Tubules - immunology; Kidney Tubules - metabolism; Male -; Mice, Inbred C57BL -; Naphthalenes - pharmacology; Neutrophil Infiltration - drug effects; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - metabolism; Phenotype -; Phenylbutyrates - pharmacology; Receptors, Prostaglandin E, EP4 Subtype - antagonists & inhibitors; Receptors, Prostaglandin E, EP4 Subtype - metabolism; Signal Transduction - drug effects
Find related publications in this database (Keywords): glomerulonephritis; immune cells; prostanoids; tubular cells