title: Anti-inflammatory effects of 5-HT3 receptor antagonists in interleukin-1beta stimulated primary human chondrocytes.
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.
authors: Universitäts-Herzzentrum Freiburg • Bad Krozingen, Abteilung für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany.
authors: Christian
authors: C
authors: Stratz
authors: Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstr. 5, D-79014 Freiburg, Germany.
authors: John
authors: J
authors: Anakwue
authors: Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstr. 5, D-79014 Freiburg, Germany.
authors: Harsharan
authors: H
authors: Bhatia
authors: Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstr. 5, D-79014 Freiburg, Germany.
authors: Stefanie
authors: S
authors: Pitz
authors: 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.
authors: Bernd L
authors: BL
authors: Fiebich
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019746:Intramolecular Oxidoreductases; D061251:Primary Cell Culture; D000071876:Prostaglandin-E Synthases; D011807:Quinolizines / Q000494:pharmacology*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*
chemical_list: D007211:Indoles; D053583:Interleukin-1beta; D015850:Interleukin-6; D011807:Quinolizines; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; C075750:8-epi-prostaglandin F2alpha; C060344:dolasetron; D015237:Dinoprost; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone
keywords: Chondrocytes; Cyclooxygenase; Cytokines; Prostaglandin E(2); Serotonin; Tropisetron