title: Effects of ketanserin on experimental colitis in mice and macrophage function.
abstract: Ketanserin is a selective 5-hydroxytryptamine (serotonin)-2A receptor (5-HT2AR) antagonist. Studies have suggested that ketanserin exerts anti-inflammatory effects independent of the baroreflex; however, the mechanisms involved remain unclear. Thus, in the present study, we aimed to evaluate the effects of ketanserin in colitis and the possible underlying mechanisms. The expression of 5-HT2AR was assessed in the colon tissues of patients with inflammatory bowel disease (IBD) and in mice with dextran sodium sulfate (DSS)-induced colitis. The therapeutic potential of ketanserin was investigated in the mice with colitis. In the colon tissue samples from the patients with IBD, a high expression level of 5-HT2AR was observed. Treatment with ketanserin attenuated the progression of experimental colitis in the mice, as indicated by body weight assessment, colon length, histological scores and cytokine release. The colonic macrophages from the ketanserin-treated mice with colitis exhibited a decreased production of inflammatory cytokines, with M2 polarization and impaired migration. The knockdown of 5-HT2AR using siRNA partly abolished the inhibitory effects of ketanserin on the release of pro-inflammatory cytokines in bone marrow derived-macrophages (BMDMs), thus demonstrating that the inhibitory effects of ketanserin on the production of inflammatory cytokines are partly dependent on 5-HT2AR. Ketanserin also inhibited the activation of nuclear factor-κB (NF-κB) in BMDMs. In conclusion, the findings of the present study demonstrate that ketanserin alleviates colitis. Its anti-inflammatory effects may be due to the promotion of the anti-inflammatory function of macrophages through 5-HT2AR/NF-κB.
authors: Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200092, P.R. China.
authors: Junhua
authors: J
authors: Xiao
authors: Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200092, P.R. China.
authors: Limei
authors: L
authors: Shao
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Jiaqing
authors: J
authors: Shen
authors: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200060, P.R. China.
authors: Weiliang
authors: W
authors: Jiang
authors: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200060, P.R. China.
authors: Yun
authors: Y
authors: Feng
authors: Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200092, P.R. China.
authors: Ping
authors: P
authors: Zheng
authors: Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200092, P.R. China.
authors: Fei
authors: F
authors: Liu
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D007650:Ketanserin / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D034741:RNA, Small Interfering; D044402:Receptor, Serotonin, 5-HT2A; D016264:Dextran Sulfate; D007650:Ketanserin