PMID- 26865503
OWN - NLM
STAT- MEDLINE
DCOM- 20161219
LR  - 20181113
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 37
IP  - 3
DP  - 2016 Mar
TI  - Effects of ketanserin on experimental colitis in mice and macrophage function.
PG  - 659-68
LID - 10.3892/ijmm.2016.2486 [doi]
AB  - 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-kappaB (NF-kappaB) 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-kappaB.
FAU - Xiao, Junhua
AU  - Xiao J
AD  - Department of Gastroenterology, Shanghai East Hospital, Tongji University, 
      Shanghai 200092, P.R. China.
FAU - Shao, Limei
AU  - Shao L
AD  - Department of Gastroenterology, Shanghai East Hospital, Tongji University, 
      Shanghai 200092, P.R. China.
FAU - Shen, Jiaqing
AU  - Shen J
AD  - Department of Gastroenterology, The First Affiliated Hospital of Soochow 
      University, Suzhou, Jiangsu 215006, P.R. China.
FAU - Jiang, Weiliang
AU  - Jiang W
AD  - Department of Gastroenterology, Shanghai First People's Hospital, Shanghai 
      Jiaotong University, Shanghai 200060, P.R. China.
FAU - Feng, Yun
AU  - Feng Y
AD  - Department of Gastroenterology, Shanghai First People's Hospital, Shanghai 
      Jiaotong University, Shanghai 200060, P.R. China.
FAU - Zheng, Ping
AU  - Zheng P
AD  - Department of Gastroenterology, Shanghai East Hospital, Tongji University, 
      Shanghai 200092, P.R. China.
FAU - Liu, Fei
AU  - Liu F
AD  - Department of Gastroenterology, Shanghai East Hospital, Tongji University, 
      Shanghai 200092, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20160210
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - 97F9DE4CT4 (Ketanserin)
SB  - IM
MH  - Animals
MH  - Colitis/chemically induced/*drug therapy/metabolism
MH  - Dextran Sulfate/pharmacology
MH  - Disease Models, Animal
MH  - Humans
MH  - Ketanserin/*therapeutic use
MH  - Macrophages/*drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/genetics/metabolism
MH  - RNA, Small Interfering
MH  - Receptor, Serotonin, 5-HT2A/genetics/metabolism
PMC - PMC4771115
EDAT- 2016/02/13 06:00
MHDA- 2016/12/20 06:00
PMCR- 2016/02/10
CRDT- 2016/02/12 06:00
PHST- 2015/11/10 00:00 [received]
PHST- 2016/02/02 00:00 [accepted]
PHST- 2016/02/12 06:00 [entrez]
PHST- 2016/02/13 06:00 [pubmed]
PHST- 2016/12/20 06:00 [medline]
PHST- 2016/02/10 00:00 [pmc-release]
AID - ijmm-37-03-0659 [pii]
AID - 10.3892/ijmm.2016.2486 [doi]
PST - ppublish
SO  - Int J Mol Med. 2016 Mar;37(3):659-68. doi: 10.3892/ijmm.2016.2486. Epub 2016 Feb 
      10.