Effects of ketanserin on experimental colitis in mice and macrophage function

Xiao,Junhua; Shao,Limei; Shen,Jiaqing; Jiang,Weiliang; Feng,Yun; Zheng,Ping; Liu,Fei

doi:10.3892/ijmm.2016.2486

Effects of ketanserin on experimental colitis in mice and macrophage function

Authors:
- Junhua Xiao
- Limei Shao
- Jiaqing Shen
- Weiliang Jiang
- Yun Feng
- Ping Zheng
- Fei Liu
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Affiliations: Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai 200092, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200060, P.R. China
Published online on: February 10, 2016 https://doi.org/10.3892/ijmm.2016.2486
Pages: 659-668
Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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