| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2540627 | International Immunopharmacology | 2014 | 7 Pages |
•The 5-HT3R antagonist dolasetron inhibits IL-1β-induced IL-6 release in chondrocytes.•Dolasetron and tropisetron prevent IL-1β-induced PGE2 synthesis in chondrocytes.•Dolasetron does not affect IL-1β-induced COX-2 and mPGES-1 expression.•Effects of dolasetron on COX-2-mediated PGE2 production may be mediated through its interaction with the peroxidation site of COX-2.
BackgroundChondrocytes 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-HT3RA) show anti-inflammatory and antioxidant properties in vitro and in vivo. Yet, the mechanisms of the anti-inflammatory effects of 5-HT3RA have not been elucidated in detail.MethodsTherefore, we examined in detail the effects of 5-HT3RA 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.ResultsWe found a significant reduction of IL-1β induced PGE2, 8-iso-PGF2β and IL-6 chondrocytes by 5-HT3RA especially by dolasetron.ConclusionsThis study provides additional support to the potential use of 5-HT3RAs as therapeutic agents to reduce joint inflammation.
