The Protective Effect of Alpha 7 Nicotinic Acetylcholine Receptor Activation on Critical Illness and Its Mechanism

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2017 Jan 27

PMID 28123345

Citations 27

Authors

Chao Ren

Ya-Lin Tong

Jun-Cong Li

Zhong-Qiu Lu

Yong-ming Yao

Affiliations

Soon will be listed here.

Abstract

Critical illnesses and injuries are recognized as major threats to human health, and they are usually accompanied by uncontrolled inflammation and dysfunction of immune response. The alpha 7 nicotinic acetylcholine receptor (α7nAchR), which is a primary receptor of cholinergic anti-inflammatory pathway (CAP), exhibits great benefits for critical ill conditions. It is composed of 5 identical α7 subunits that form a central pore with high permeability for calcium. This putative structure is closely associated with its functional states. Activated α7nAChR exhibits extensive anti-inflammatory and immune modulatory reactions, including lowered pro-inflammatory cytokines levels, decreased expressions of chemokines as well as adhesion molecules, and altered differentiation and activation of immune cells, which are important in maintaining immune homeostasis. Well understanding of the effects and mechanisms of α7nAChR will be of great value in exploring effective targets for treating critical diseases.

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References

Reiss L, Uhlig U, Uhlig S . Models and mechanisms of acute lung injury caused by direct insults. Eur J Cell Biol. 2012; 91(6-7):590-601. DOI: 10.1016/j.ejcb.2011.11.004. View

Lieberman J, Dunbar G, Segreti A, Girgis R, Seoane F, Beaver J . A randomized exploratory trial of an α-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia. Neuropsychopharmacology. 2013; 38(6):968-75. PMC: 3629385. DOI: 10.1038/npp.2012.259. View

Terrando N, Yang T, Ryu J, Newton P, Monaco C, Feldmann M . Stimulation of the α7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. Mol Med. 2014; 20:667-75. PMC: 4398668. DOI: 10.2119/molmed.2014.00143. View

Fujii T, Horiguchi K, Sunaga H, Moriwaki Y, Misawa H, Kasahara T . SLURP-1, an endogenous α7 nicotinic acetylcholine receptor allosteric ligand, is expressed in CD205(+) dendritic cells in human tonsils and potentiates lymphocytic cholinergic activity. J Neuroimmunol. 2013; 267(1-2):43-9. DOI: 10.1016/j.jneuroim.2013.12.003. View

Johnson E, Matthay M . Acute lung injury: epidemiology, pathogenesis, and treatment. J Aerosol Med Pulm Drug Deliv. 2010; 23(4):243-52. PMC: 3133560. DOI: 10.1089/jamp.2009.0775. View

Li Q, Zhou X, Kolosov V, Perelman J . Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells. Cell Physiol Biochem. 2011; 27(5):605-12. DOI: 10.1159/000329982. View

Albuquerque E, Pereira E, Alkondon M, Rogers S . Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol Rev. 2009; 89(1):73-120. PMC: 2713585. DOI: 10.1152/physrev.00015.2008. View

Xu M, Scott J, Liu K, Bishop H, Renaud D, Palmer R . The influence of nicotine on granulocytic differentiation - inhibition of the oxidative burst and bacterial killing and increased matrix metalloproteinase-9 release. BMC Cell Biol. 2008; 9:19. PMC: 2375863. DOI: 10.1186/1471-2121-9-19. View

Kobayashi K, Hernandez L, Galan J, Janeway Jr C, Medzhitov R, Flavell R . IRAK-M is a negative regulator of Toll-like receptor signaling. Cell. 2002; 110(2):191-202. DOI: 10.1016/s0092-8674(02)00827-9. View

10.

Ji B, Gaiser S, Chen X, Ernst S, Logsdon C . Intracellular trypsin induces pancreatic acinar cell death but not NF-kappaB activation. J Biol Chem. 2009; 284(26):17488-98. PMC: 2719389. DOI: 10.1074/jbc.M109.005520. View

11.

Lu B, Kwan K, Levine Y, Olofsson P, Yang H, Li J . α7 nicotinic acetylcholine receptor signaling inhibits inflammasome activation by preventing mitochondrial DNA release. Mol Med. 2014; 20:350-8. PMC: 4153835. DOI: 10.2119/molmed.2013.00117. View

12.

Tracey K . Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 2007; 117(2):289-96. PMC: 1783813. DOI: 10.1172/JCI30555. View

13.

Su X, Lee J, Matthay Z, Mednick G, Uchida T, Fang X . Activation of the alpha7 nAChR reduces acid-induced acute lung injury in mice and rats. Am J Respir Cell Mol Biol. 2007; 37(2):186-92. PMC: 1976545. DOI: 10.1165/rcmb.2006-0240OC. View

14.

Tyagi E, Agrawal R, Nath C, Shukla R . Cholinergic protection via alpha7 nicotinic acetylcholine receptors and PI3K-Akt pathway in LPS-induced neuroinflammation. Neurochem Int. 2009; 56(1):135-42. DOI: 10.1016/j.neuint.2009.09.011. View

15.

Kox M, van Velzen J, Pompe J, Hoedemaekers C, van der Hoeven J, Pickkers P . GTS-21 inhibits pro-inflammatory cytokine release independent of the Toll-like receptor stimulated via a transcriptional mechanism involving JAK2 activation. Biochem Pharmacol. 2009; 78(7):863-72. DOI: 10.1016/j.bcp.2009.06.096. View

16.

Pavlov V, Tracey K . Controlling inflammation: the cholinergic anti-inflammatory pathway. Biochem Soc Trans. 2006; 34(Pt 6):1037-40. DOI: 10.1042/BST0341037. View

17.

Larroche C, Mouthon L . Pathogenesis of hemophagocytic syndrome (HPS). Autoimmun Rev. 2004; 3(2):69-75. DOI: 10.1016/S1568-9972(03)00091-0. View

18.

Peck-Palmer O, Unsinger J, Chang K, McDonough J, Perlman H, McDunn J . Modulation of the Bcl-2 family blocks sepsis-induced depletion of dendritic cells and macrophages. Shock. 2008; 31(4):359-66. PMC: 2778022. DOI: 10.1097/SHK.0b013e31818ba2a2. View

19.

M Greene C, Ramsay H, Wells R, ONeill S, McElvaney N . Inhibition of Toll-like receptor 2-mediated interleukin-8 production in Cystic Fibrosis airway epithelial cells via the alpha7-nicotinic acetylcholine receptor. Mediators Inflamm. 2010; 2010:423241. PMC: 2850130. DOI: 10.1155/2010/423241. View

20.

Pavlov V, Ochani M, Yang L, Gallowitsch-Puerta M, Ochani K, Lin X . Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med. 2007; 35(4):1139-44. DOI: 10.1097/01.CCM.0000259381.56526.96. View