Role of α7-Nicotinic Acetylcholine Receptor in Regulating Anti-Inflammatory Response of Animals

  • WU Pei ,
  • FENG Lin ,
  • JIANG Weidang ,
  • ZHOU Xiaoqiu
Expand
  • 1. Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China;
    2. Key Laboratory of Animal Disease-Resistant Nutrition, Ministry of Education, Chengdu 611130, China

Received date: 2021-04-26

  Online published: 2021-11-10

Supported by

 

Abstract

α7-nicotinic acetylcholine receptor (α7nAChR) is a ligand-gated ion channel protein and consists of five α7 subunits. Besides neurocyte, α7nAChR also expresses in several immune cells. Activating α7nAChR could attenuate inflammatory response by modulating gene expression, protein synthesis of cytokines mainly through nuclear factor-kappa B (NF-κB) and Janus kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) signalling pathways. Several nutrients could regulate inflammation through α7nAChR signaling. This review focused on the underlying mechanisms of anti-inflammation effects mediated by α7nAChR and the role of α7nAChR in inflammatory regulation of nutrients.

Cite this article

WU Pei , FENG Lin , JIANG Weidang , ZHOU Xiaoqiu . Role of α7-Nicotinic Acetylcholine Receptor in Regulating Anti-Inflammatory Response of Animals[J]. Chinese Journal of Animal Nutrition, 2021 , 33(11) : 6001 -6008 . DOI: 10.3969/j.issn.1006-267x.2021.11.001

References

[1] TAGA I, LAN C Q, ALTOSAAR I.Plant essential oils and mastitis disease:their potential inhibitory effects on pro-inflammatory cytokine production in response to bacteria related inflammation[J].Natural Product Communications, 2012, 7(5):675-682.
[2] GRILLI E, TUGNOLI B, PASSEY J L, et al.Impact of dietary organic acids and botanicals on intestinal integrity and inflammation in weaned pigs[J].BMC Veterinary Research, 2015, 11:96.
[3] DE JONGE W J, ULLOA L.The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation[J].British Journal of Pharmacology, 2007, 151(7):915-929.  
[4] KOHOUTOVA M, HORAK J, JARKOVSKA D, et al.Vagus nerve stimulation attenuates multiple organ dysfunction in resuscitated porcine progressive sepsis[J].Critical Care Medicine, 2019, 47(6):e461-e469.
[5] POHL C S, LENNON E M, LI Y H, et al.Typhimurium challenge in juvenile pigs modulates the expression and localization of enteric cholinergic proteins and correlates with mucosal injury and inflammation[J].Autonomic Neuroscience, 2018, 213:51-59.
[6] JANA B, CAŁKA J, PALUS K, et al.Escherichia coli-induced inflammation changes the expression of acetylcholine receptors (M2R, M3R, and α-7nAChR) in the pig uterus[J].Journal of Veterinary Research, 2020, 64(4):531-541.  
[7] LIU Z Q, WANG L L, LV Z, et al.The cholinergic and adrenergic autocrine signaling pathway mediates immunomodulation in oyster Crassostrea gigas[J].Frontiers in Immunology, 2018, 9:284.
[8] WANG H, YU M, OCHANI M, et al.Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation[J].Nature, 2003, 421:384-388.
[9] GAULT J, ROBINSON M, BERGER R, et al.Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7)[J].Genomics, 1998, 52(2):173-185.  
[10] SÉGUÉLA P, WADICHE J, DINELEY-MILLER K, et al.Molecular cloning, functional properties, and distribution of rat brain alpha 7:a nicotinic cation channel highly permeable to calcium[J].Journal of Neuroscience, 1993, 13(2):596-604.  
[11] COUTURIER S, BERTRAND D, MATTER J M, et al.A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX[J].Neuron, 1990, 5(6):847-856.  
[12] ZIRGER J M, BEATTIE C E, MCKAY D B, et al.Cloning and expression of zebrafish neuronal nicotinic acetylcholine receptors[J].Gene Expression Patterns, 2003, 3(6):747-754.  
[13] FUJII T, MASHIMO M, MORIWAKI Y, et al.Expression and function of the cholinergic system in immune cells[J].Frontiers in Immunology, 2017, 8:1085.
[14] TRUONG L D, TROSTEL J, GARCIA G E.Absence of nicotinic acetylcholine receptor α7 subunit amplifies inflammation and accelerates onset of fibrosis:an inflammatory kidney model[J].The FASEB Journal, 2015, 29(8):3558-3570.  
[15] SHAO B Z, WANG S L, FANG J, et al.Alpha7 nicotinic acetylcholine receptor alleviates inflammatory bowel disease through induction of AMPK-mTOR-p70S6K-mediated autophagy[J].Inflammation, 2019, 42(5):1666-1679.  
[16] HUANG D Y, LI Q, SHI C Y, et al.Dexmedetomidine attenuates inflammation and pancreatic injury in a rat model of experimental severe acute pancreatitis via cholinergic anti-inflammatory pathway[J].Chinese Medical Journal, 2020, 133(9):1073-1079.  
[17] ZI S F, LI J H, LIU L, et al.Dexmedetomidine-mediated protection against septic liver injury depends on TLR4/MyD88/NF-κB signaling down regulation partly via cholinergic anti-inflammatory mechanisms[J].International Immunopharmacology, 2019, 76:105898.
[18] TENG P, LIU Y, DAI Y, et al.Nicotine attenuates osteoarthritis pain and matrix metalloproteinase-9 expression via the α7 nicotinic acetylcholine receptor[J].Journal of Immunology, 2019, 203(2):485-492.  
[19] TASAKA Y, YASUNAGA D, KIYOI T, et al.Involvement of stimulation of α7 nicotinic acetylcholine receptors in the suppressive effect of tropisetron on dextran sulfate sodium-induced colitis in mice[J].Journal of Pharmacological Sciences, 2015, 127(3):275-283.  
[20] ZHANG Y, ZHOU F, WANG Z L, et al.PNU-282987 attenuates intestinal epithelial barrier dysfunction in LPS-induced endotoxemia[J].Inflammation, 2020, 43(2):417-424.  
[21] SHAO Z Z, LI Q, WANG S, et al.Protective effects of PNU-282987 on sepsis-induced acute lung injury in mice[J].Molecular Medicine Reports, 2019, 19(5):3791-3798.
[22] ZHAO X, YU Z Z, LV Z, et al.Activation of alpha-7 nicotinic acetylcholine receptors (α7nAchR) promotes the protective autophagy in LPS-induced acute lung injury (ALI) in vitro and in vivo[J].Inflammation, 2019, 42(6):2236-2245.  
[23] LOPES F, GRAEPEL R, REYES J L, et al.Involvement of mast cells in α7 nicotinic receptor agonist exacerbation of freund's complete adjuvant-induced monoarthritis in mice[J].Arthritis & Rheumatology, 2016, 68(2):542-552.  
[24] LYKHMUS O, KALASHNYK O, KOVAL L, et al.Mesenchymal stem cells or interleukin-6 improve episodic memory of mice lacking α7 nicotinic acetylcholine receptors[J].Neuroscience, 2019, 413:31-44.
[25] 宫丽荣, 董树安, 阚永星, 等.α7烟碱型乙酰胆碱受体在电针减轻肢体缺血再灌注兔肺损伤中的作用[J].中国中西医结合外科杂志, 2019, 25(4):443-447. GONG L R, DONG S A, KAN Y X, et al.Effect of α7nAChR in electroacupuncture-induced reduction of lung injury induced by limb ischemia-reperfusion in rabbits[J].Chinese Journal of Surgery of Integrated Traditional and Western Medicine, 2019, 25(4):443-447.(in Chinese)
[26] GODIN J R, ROY P, QUADRI M, et al.A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE[J].Brain, Behavior, and Immunity, 2020, 87:286-300.
[27] KASHIWAGI S, KHAN M A S, YASUHARA S, et al.Prevention of burn-induced inflammatory responses and muscle wasting by GTS-21, a specific agonist for α7 nicotinic acetylcholine receptors[J].Shock, 2017, 47(1):61-69.  
[28] DENG Y, GUO S L, WEI B, et al.Activation of nicotinic acetylcholine α7 receptor attenuates progression of monocrotaline-induced pulmonary hypertension in rats by down regulating the NLRP3 inflammasome[J].Frontiers in Pharmacology, 2019, 10:128.
[29] SCABIA G, CANCELLO R, DALLANOCE C, et al.ICH3, a selective alpha7 nicotinic acetylcholine receptor agonist, modulates adipocyte inflammation associated with obesity[J].Journal of Endocrinological Investigation, 2020, 43(7):983-993.  
[30] PATEL H, MCINTIRE J, RYAN S, et al.Anti-inflammatory effects of astroglial α7 nicotinic acetylcholine receptors are mediated by inhibition of the NF-κB pathway and activation of the Nrf2 pathway[J].Journal of Neuroinflammation, 2017, 14(1):192.
[31] YUE Y, LIU R X, CHENG W X, et al.GTS-21 attenuates lipopolysaccharide-induced inflammatory cytokine production in vitro by modulating the Akt and NF-κB signaling pathway through the α7 nicotinic acetylcholine receptor[J].International Immunopharmacology, 2015, 29(2):504-512.  
[32] FANG J Y, WANG J W, CHEN F H, et al.α7nAChR deletion aggravates myocardial infarction and enhances systemic inflammatory reaction via mTOR-signaling-related autophagy[J].Inflammation, 2019, 42(4):1190-1202.  
[33] ALZAREA S, RAHMAN S.Alpha-7 nicotinic receptor allosteric modulator PNU120596 prevents lipopolysaccharide-induced anxiety, cognitive deficit and depression-like behaviors in mice[J].Behavioural Brain Research, 2019, 366:19-28.
[34] YANG X, ZHAO C, CHEN X, et al.Monocytes primed with GTS-21/α7 nAChR (nicotinic acetylcholine receptor) agonist develop anti-inflammatory memory[J].QJM, 2017, 110(7):437-445.
[35] LI L, LIU Z, JIANG Y Y, et al.Acetylcholine suppresses microglial inflammatory response via α7nAChR to protect hippocampal neurons[J].Journal of Integrative Neuroscience, 2019, 18(1):51-56.
[36] MASHIMO M, FUJII T, ONO S, et al.Minireview:divergent roles of α7 nicotinic acetylcholine receptors expressed on antigen-presenting cells and CD4+ T cells in the regulation of T cell differentiation[J].International Immunopharmacology, 2020, 82:106306.
[37] SHI S, LIANG D L, BAO M, et al.Gx-50 inhibits neuroinflammation via α7nAChR activation of the JAK2/STAT3 and PI3K/AKT pathways[J].Journal of Alzheimers Disease, 2016, 50(3):859-871.  
[38] KONG W L, KANG K, GAO Y, et al.GTS-21 protected against LPS-induced sepsis myocardial injury in mice through α7nAChR[J].Inflammation, 2018, 41(3):1073-1083.  
[39] XU H M, SHI Q Y, MO Y X, et al.Downregulation of α7 nicotinic acetylcholine receptors in peripheral blood monocytes is associated with enhanced inflammation in preeclampsia[J].BMC Pregnancy and Childbirth, 2019, 19(1):188.
[40] WU J, JIAO Z Y, ZHANG Z, et al.Cross-talk between α7nAChR-mediated cholinergic pathway and acylation stimulating protein signaling in 3T3-L1 adipocytes:role of NF-κB and STAT3[J].Biochemistry and Cell Biology, 2015, 93(4):335-342.  
[41] ZHANG X F, XIANG S Y, GENG W Y, et al.Electro-acupuncture regulates the cholinergic anti-inflammatory pathway in a rat model of chronic obstructive pulmonary disease[J].Journal of Integrative Medicine, 2018, 16(6):418-426.  
[42] HAN R L, ZHANG G H, QIAO X L, et al.α7 nicotinic acetylcholine receptor mediates the neuroprotection of remote ischemic postconditioning in a rat model of asphyxial cardiac arrest[J].Journal of Surgical Research, 2020, 246:6-18.
[43] LI Q, ZHOU X D, KOLOSOV V P, et al.Nicotine reduces TNF-α expression through a α7nAChR/MyD88/NF-κB pathway in HBE16 airway epithelial cells[J].Cellular Physiology and Biochemistry, 2011, 27(5):605-612.  
[44] CHEN K Y, SUN Y J, DIAO Y G, et al.α7 nicotinic acetylcholine receptor agonist inhibits the damage of rat hippocampal neurons by TLR4/Myd88/NF-κB signaling pathway during cardiopulmonary bypass[J].Molecular Medicine Reports, 2017, 16(4):4770-4776.  
[45] DE JONGE W J, VAN DER ZANDEN E P, THE F O, et al.Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway[J].Nature Immunology, 2005, 6(8):844-851.  
[46] SMEDLUND K, TANO J Y, MARGIOTTA J, et al.Evidence for operation of nicotinic and muscarinic acetylcholine receptor-dependent survival pathways in human coronary artery endothelial cells[J].Journal of Cellular Biochemistry, 2011, 112(8):1978-1984.  
[47] TAKAHASHI H K, IWAGAKI H, HAMANO R, et al.Alpha7 nicotinic acetylcholine receptor stimulation inhibits lipopolysaccharide-induced interleukin-18 and -12 production in monocytes[J].Journal of Pharmacological Sciences, 2006, 102(1):143-146.  
[48] NIIJIMA A, MEGUID M M.Influence of systemic arginine-lysine on immune organ function:an electrophysiological study[J].Brain Research Bulletin, 1998, 45(5):437-441.  
[49] LUBBERS T, DE HAAN J J, LUYER M D P, et al.Cholecystokinin/cholecystokinin-1 receptor-mediated peripheral activation of the afferent vagus by enteral nutrients attenuates inflammation in rats[J].Annals of Surgery, 2010, 252(2):376-382.  
[50] LUYER M D, GREVE J W M, HADFOUNE M, et al.Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve[J].Journal of Experimental Medicine, 2005, 202(8):1023-1029.  
[51] QI Y, SI D, ZHU L, et al.High-fat diet-induced obesity affects alpha 7 nicotine acetylcholine receptor expressions in mouse lung myeloid cells[J].Scientific Reports, 2020, 10:18368.
[52] COSTA S O, SOUZA C M, LANZA P G, et al.Maternal high fat diet consumption reduces liver alpha7 nicotinic cholinergic receptor expression and impairs insulin signalling in the offspring[J].Scientific Reports, 2020, 10:48.
[53] MORGANSTERN I, YE Z, LIANG S, et al.Involvement of cholinergic mechanisms in the behavioral effects of dietary fat consumption[J].Brain Research, 2012, 1470:24-34.
[54] PUCCI S, FASOLI F, MORETTI M, et al.Choline and nicotine increase glioblastoma cell proliferation by binding and activating α7- and α9- containing nicotinic receptors[J].Pharmacological Research, 2021, 163:105336.
[55] GUSEVA M V, HOPKINS D M, SCHEFF S W, et al.Dietary choline supplementation improves behavioral, histological, and neurochemical outcomes in a rat model of traumatic brain injury[J].Journal of Neurotrauma, 2008, 25(8):975-983.  
[56] ZHANG M, HAN X J, BAO J E, et al.Choline supplementation during pregnancy protects against gestational lipopolysaccharide-induced inflammatory responses[J].Reproductive Sciences, 2018, 25(1):74-85.  
[57] 余军, 赵维星, 杜春彦, 等.胆碱改善脂多糖诱导的小鼠中枢神经系统炎症反应及认知功能障碍[J].南方医科大学学报, 2017, 37(5):600-606. YU J, ZHAO W X, DU C Y, et al.Choline improves lipopolysaccharide-induced central nervous system inflammatory response and cognitive dysfunction in mice[J].Journal of Southern Medical University, 2017, 37(5):600-606.(in Chinese)
[58] PARRISH W R, ROSAS-BALLINA M, GALLOWITSCH-PUERTA M, et al.Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor-mediated signaling[J].Molecular Medicine, 2008, 14(9/10):567-574.
[59] WEI X M, YANG W, LIU L X, et al.Effects of L-arginine and N(ω)-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats[J].Neuroscience Bulletin, 2013, 29(3):303-310.  
[60] KUMAR P T, ANTONY S, NANDHU M S, et al.Vitamin D3 restores altered cholinergic and insulin receptor expression in the cerebral cortex and muscarinic M3 receptor expression in pancreatic islets of streptozotocin induced diabetic rats[J].The Journal of Nutritional Biochemistry, 2011, 22(5):418-425.  
[61] PEEYUSH K T, SAVITHA B, SHERIN A, et al.Cholinergic, dopaminergic and insulin receptors gene expression in the cerebellum of streptozotocin-induced diabetic rats:functional regulation with vitamin D3 supplementation[J].Pharmacology Biochemistry and Behavior, 2010, 95(2):216-222.  
[62] KIMURA K, INABA Y, WATANABE H, et al.Nicotinic alpha-7 acetylcholine receptor deficiency exacerbates hepatic inflammation and fibrosis in a mouse model of non-alcoholic steatohepatitis[J].Journal of Diabetes Investigation, 2019, 10(3):659-666.  
[63] GUIJARRO A, LAVIANO A, MEGUID M M.Hypothalamic integration of immune function and metabolism[J].Progress in Brain Research, 2006, 153:367-405.
[64] DUFRESNE M, SEVA C, FOURMY D.Cholecystokinin and gastrin receptors[J].Physiological Reviews, 2006, 86(3):805-847.  
Outlines

/