Christian Stratz1, John Anakwue2, Harsharan Bhatia2, Stefanie Pitz2, Bernd L Fiebich3. 1. Universitäts-Herzzentrum Freiburg • Bad Krozingen, Abteilung für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany. 2. Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstr. 5, D-79014 Freiburg, Germany. 3. Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstr. 5, D-79014 Freiburg, Germany; VivaCell Biotechnology GmbH, Ferdinand-Porsche-Str. 5, D-79211 Denzlingen, Germany. Electronic address: bernd.fiebich@uniklinik-freiburg.de.
Abstract
BACKGROUND: Chondrocytes are one of the main cell types involved in rheumatoid inflammation, releasing mediators which add to cartilage destruction, bone damage and consequently disability. Current evidence suggests that serotonin 5-HT(3) receptor antagonists (5-HT(3)RA) show anti-inflammatory and antioxidant properties in vitro and in vivo. Yet, the mechanisms of the anti-inflammatory effects of 5-HT(3)RA have not been elucidated in detail. METHODS: Therefore, we examined in detail the effects of 5-HT(3)RA on inflammatory parameters in human primary chondrocytes in vitro by studying prostaglandin E2 (PGE2) and 8-isoprostane (8-iso-PGF2α) levels by EIA and interleukin-6 (IL-6) synthesis by ELISA. Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) protein levels were analyzed by Western blot. RESULTS: We found a significant reduction of IL-1β induced PGE2, 8-iso-PGF2β and IL-6 chondrocytes by 5-HT(3)RA especially by dolasetron. CONCLUSIONS: This study provides additional support to the potential use of 5-HT(3)RAs as therapeutic agents to reduce joint inflammation.
BACKGROUND: Chondrocytes are one of the main cell types involved in rheumatoid inflammation, releasing mediators which add to cartilage destruction, bone damage and consequently disability. Current evidence suggests that serotonin 5-HT(3) receptor antagonists (5-HT(3)RA) show anti-inflammatory and antioxidant properties in vitro and in vivo. Yet, the mechanisms of the anti-inflammatory effects of 5-HT(3)RA have not been elucidated in detail. METHODS: Therefore, we examined in detail the effects of 5-HT(3)RA on inflammatory parameters in human primary chondrocytes in vitro by studying prostaglandin E2 (PGE2) and 8-isoprostane (8-iso-PGF2α) levels by EIA and interleukin-6 (IL-6) synthesis by ELISA. Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) protein levels were analyzed by Western blot. RESULTS: We found a significant reduction of IL-1β induced PGE2, 8-iso-PGF2β and IL-6 chondrocytes by 5-HT(3)RA especially by dolasetron. CONCLUSIONS: This study provides additional support to the potential use of 5-HT(3)RAs as therapeutic agents to reduce joint inflammation.
Authors: Jia Yi Guo; Feng Li; Yong Bing Wen; Hong Xun Cui; Ma Long Guo; Lin Zhang; Yun Fei Zhang; Yan Jin Guo; Yan Xing Guo Journal: Oncotarget Date: 2017-06-03