Stratz Christian, Anakwue John, Bhatia Harsharan, Pitz Stefanie, Fiebich Bernd L
Universitäts-Herzzentrum Freiburg • Bad Krozingen, Abteilung für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany.
Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstr. 5, D-79014 Freiburg, Germany.
Int Immunopharmacol. 2014 Sep;22(1):160-6. doi: 10.1016/j.intimp.2014.06.003. Epub 2014 Jun 27.
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.
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.
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.
This study provides additional support to the potential use of 5-HT(3)RAs as therapeutic agents to reduce joint inflammation.
软骨细胞是参与类风湿性炎症的主要细胞类型之一，可释放加重软骨破坏、骨损伤并最终导致残疾的介质。目前的证据表明，5-羟色胺5-HT(3)受体拮抗剂（5-HT(3)RA）在体外和体内均具有抗炎和抗氧化特性。然而，5-HT(3)RA抗炎作用的机制尚未完全阐明。
因此，我们通过酶免疫分析（EIA）研究前列腺素E2（PGE2）和8-异前列腺素（8-iso-PGF2α）水平，并通过酶联免疫吸附测定（ELISA）检测白细胞介素-6（IL-6）的合成，详细研究了5-HT(3)RA对人原代软骨细胞炎症参数的影响。通过蛋白质印迹法分析环氧化酶-2（COX-2）和微粒体前列腺素E合酶-1（mPGES-1）的蛋白水平。
我们发现5-HT(3)RA，尤其是多潘立酮，可显著降低IL-1β诱导的软骨细胞中PGE2、8-iso-PGF2β和IL-6的水平。
本研究为5-HT(3)RA作为减轻关节炎症的治疗药物的潜在用途提供了更多支持。
