Anti-inflammatory effects of 5-HT3 receptor antagonists in interleukin-1beta stimulated primary human chondrocytes

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-HT3 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 (PGE(2)) and 8-isoprostane (8-iso-PGF(2 alpha)) 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-1 beta induced PGE(2), 8-iso-PGF(2 beta) and IL-6 chondrocytes by 5-HT(3)RA especially by dolasetron. Conclusions: This study provides additional support to the potential use of 5-HT3RAs as therapeutic agents to reduce joint inflammation. (C) 2014 Elsevier B.V. All rights reserved.