PMID- 31236857
OWN - NLM
STAT- MEDLINE
DCOM- 20200219
LR  - 20211204
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 42
IP  - 5
DP  - 2019 Oct
TI  - Alpha7 Nicotinic Acetylcholine Receptor Alleviates Inflammatory Bowel Disease 
      Through Induction of AMPK-mTOR-p70S6K-Mediated Autophagy.
PG  - 1666-1679
LID - 10.1007/s10753-019-01027-9 [doi]
AB  - Alpha7 nicotinic acetylcholine receptor (alpha7nAChR) has been reported to be 
      protective in several kinds of disorders through inflammatory suppression. Here, 
      we investigated the role of alpha7nAChR in inflammatory bowel disease (IBD) on 
      alpha7nAChR deficient mice (alpha7nAChR(-/-)) and the wild-type mice (alpha7nAChR(+/+)). 
      Three percent dextran sulfate sodium (DSS) was used for the creation of IBD mice 
      model and lipopolysaccharides (LPS)/DSS as an inflammatory stressor in murine 
      bone marrow-derived macrophages (BMDMs). The severity of IBD was determined and 
      HE staining as well as enzyme-linked immunosorbent assay (ELISA) and real-time 
      PCR were used to detect the level of inflammatory activation. Western blot was 
      used to determine the levels of autophagy-related proteins. Transmission electron 
      microscopy and mRFP-GFP-LC3 plasmid were applied to determine the levels of 
      autophagy. We demonstrated that deficiency in alpha7nAChR produced a detrimental 
      effect on IBD severity and inflammatory reaction in DSS-induced colitis models. 
      Those effects were led to via autophagy dysfunction. alpha7nAChR deficiency 
      attenuated the protective and anti-inflammatory effect of autophagy inducer in 
      IBD mice and BMDMs challenged with LPS/DSS. The alleviative effect of activating 
      alpha7nAChR was attenuated through inhibiting adenosine 5'-monophosphate 
      (AMP)-activated protein kinase (AMPK)-mediated signaling. In conclusion, alpha7nAChR 
      contributes to alleviate IBD through the induction of AMPK-mammalian target of 
      rapamycin rabbit (mTOR)-p70 ribosomal protein S6 kinase (p70S6K)-mediated 
      autophagy, thus providing a novel target for the treatment of IBD.
FAU - Shao, Bo-Zong
AU  - Shao BZ
AD  - Department of Gastroenterology, General Hospital of the Chinese People's 
      Liberation Army, Beijing, China. shaobozong@126.com.
FAU - Wang, Shu-Ling
AU  - Wang SL
AD  - Department of Gastroenterology, Changhai Hospital, Second Military Medical 
      University/Naval Medical University, Shanghai, China.
FAU - Fang, Jun
AU  - Fang J
AD  - Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 
      China.
FAU - Li, Zhao-Shen
AU  - Li ZS
AD  - Department of Gastroenterology, Changhai Hospital, Second Military Medical 
      University/Naval Medical University, Shanghai, China. lizhaoshen1956@163.com.
FAU - Bai, Yu
AU  - Bai Y
AD  - Department of Gastroenterology, Changhai Hospital, Second Military Medical 
      University/Naval Medical University, Shanghai, China. baiyu1998@hotmail.com.
FAU - Wu, Kai
AU  - Wu K
AD  - Department of Gastroenterology, General Hospital of the Chinese People's 
      Liberation Army, Beijing, China. wukai@126.com.
LA  - eng
GR  - 81670473/National Natural Science Foundation of China/
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Inflammatory Bowel Diseases/*prevention & control
MH  - Mice
MH  - Mice, Knockout
MH  - Rabbits
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Transcriptional Activation
MH  - alpha7 Nicotinic Acetylcholine Receptor/*physiology
OTO - NOTNLM
OT  - alpha7 nicotinic acetylcholine receptor
OT  - autophagy
OT  - dextran sulfate sodium
OT  - inflammatory bowel disease
OT  - lipopolysaccharides
EDAT- 2019/06/27 06:00
MHDA- 2020/02/20 06:00
CRDT- 2019/06/26 06:00
PHST- 2019/06/27 06:00 [pubmed]
PHST- 2020/02/20 06:00 [medline]
PHST- 2019/06/26 06:00 [entrez]
AID - 10.1007/s10753-019-01027-9 [pii]
AID - 10.1007/s10753-019-01027-9 [doi]
PST - ppublish
SO  - Inflammation. 2019 Oct;42(5):1666-1679. doi: 10.1007/s10753-019-01027-9.