PMID- 27938563
OWN - NLM
STAT- MEDLINE
DCOM- 20170925
LR  - 20181202
IS  - 1007-3418 (Print)
IS  - 1007-3418 (Linking)
VI  - 24
IP  - 10
DP  - 2016 Oct 20
TI  - [Effect of nicotinic acetylcholine receptor alpha7 subunit gene on liver inflammatory 
      reaction in mice with nonalcoholic steatohepatitis and related mechanisms].
PG  - 767-771
LID - 10.3760/cma.j.issn.1007-3418.2016.10.010 [doi]
AB  - Objective: To investigate the effect of nicotinic acetylcholine receptor alpha7 
      (alpha7nAChR) subunit gene on liver inflammation in mice with nonalcoholic 
      steatohepatitis (NASH) and related mechanisms. Methods: C57BL/6J mice and alpha7nAChR 
      gene knockout mice were fed for 24 weeks to establish the NASH model, and the 
      mice were sacrificed to isolate and culture the primary liver macrophages. After 
      the treatment with nicotine and endotoxin, ELISA was used to measure the levels 
      of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-alpha 
      (TNF-alpha) in supernatant; indirect immunofluorescence assay and Western blot were 
      used to observe the effect on the NF-kappaB signaling pathway, and quantitative PCR 
      was used to measure the mRNA expression of Toll-like receptor-4 (TLR-4) in 
      macrophages. An analysis of variance was used for comparison of means between 
      multiple groups. Results: The results of ELISA showed that compared with the 
      endotoxin+nicotine group of C57 NASH mice, the endotoxin+nicotine group of gene 
      knockout NASH mice had significantly higher levels of IL-6 and TNF-alpha in 
      supernatant (IL-6: 1 599+/-65 pg/ml vs 1 465+/-45 pg/ml, P < 0.05; TNF-alpha: 1 567+/-66 
      pg/ml vs 1 433+/-50 pg/ml, P < 0.05). The results of Western blot showed that 
      compared with the endotoxin+nicotine group of C57 NASH mice, the 
      endotoxin+nicotine group of gene knockout NASH mice had significantly higher 
      relative protein expression of phosphorylated NF-kappaB and TLR-4 (NF-kappaB: 69 425+/-600 
      vs 51 133+/-200, P < 0.05; TLR-4: 93 387+/-684 vs 64 198+/-630, P < 0.05). The results 
      of indirect immunofluorescence assay showed that the endotoxin+nicotine group of 
      gene knockout NASH mice had a significantly higher fluorescence intensity of 
      NF-kappaB than the endotoxin+nicotine group of C57 NASH mice. The results of PCR 
      showed that the endotoxin+nicotine group of gene knockout NASH mice had 
      significantly higher relative mRNA expression of TLR-4 than the 
      endotoxin+nicotine group of C57 NASH mice (4.13+/-0.13 vs 2.93+/-0.14, P < 0.05). 
      Conclusion: The alpha7nAChR gene knockout can aggravate the degree of inflammatory 
      reaction in NASH, and its mechanism may be related to the fact that the NF-kappaB 
      signaling pathway cannot be inhibited, which aggravates inflammatory reaction.
FAU - Li, F Q
AU  - Li FQ
AD  - Department of Infectious Diseases, The Center Hospital of Shaoxing, Shaoxing 
      312030, China.
FAU - Wu, X C
AU  - Wu XC
AD  - The Second Clinical Medial College, Zhejiang Chinese Medical University, Hangzhou 
      310053, China.
FAU - Xu, L N
AU  - Xu LN
AD  - The Second Clinical Medial College, Zhejiang Chinese Medical University, Hangzhou 
      310053, China.
FAU - Chen, X M
AU  - Chen XM
AD  - Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang 
      Chinese Medical University, Hangzhou 310005, China.
FAU - Lu, S
AU  - Lu S
AD  - The Second Clinical Medial College, Zhejiang Chinese Medical University, Hangzhou 
      310053, China.
FAU - Tang, C L
AU  - Tang CL
AD  - Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang 
      Chinese Medical University, Hangzhou 310005, China.
LA  - chi
PT  - Journal Article
PL  - China
TA  - Zhonghua Gan Zang Bing Za Zhi
JT  - Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of 
      hepatology
JID - 9710009
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Endotoxins)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Disease Models, Animal
MH  - Endotoxins/*therapeutic use
MH  - Hepatitis
MH  - *Inflammation/drug therapy/immunology
MH  - Interleukin-6/immunology
MH  - Liver/*drug effects/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B
MH  - Nicotine/*therapeutic use
MH  - Nicotinic Agonists/*therapeutic use
MH  - Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/immunology
MH  - Phosphorylation
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/immunology
MH  - alpha7 Nicotinic Acetylcholine Receptor/*agonists/immunology
EDAT- 2016/12/13 06:00
MHDA- 2017/09/26 06:00
CRDT- 2016/12/13 06:00
PHST- 2016/12/13 06:00 [entrez]
PHST- 2016/12/13 06:00 [pubmed]
PHST- 2017/09/26 06:00 [medline]
AID - 10.3760/cma.j.issn.1007-3418.2016.10.010 [doi]
PST - ppublish
SO  - Zhonghua Gan Zang Bing Za Zhi. 2016 Oct 20;24(10):767-771. doi: 
      10.3760/cma.j.issn.1007-3418.2016.10.010.