REVIEW PAPER
Role of α7 nicotinic receptor in the immune system and intracellular signaling pathways
Submission date: 2015-04-02
Acceptance date: 2015-05-13
Publication date: 2015-10-15
Cent Eur J Immunol 2015;40(3):373-379
KEYWORDS
ABSTRACT
Acetylcholine has been well known as one of the most exemplary neurotransmitters. In humans, this versatile molecule and its synthesizing enzyme, choline acetyltransferase, have been found in various non-neural tissues such as the epithelium, endothelium, mesothelium muscle, blood cells and immune cells. The non-neuronal acetylcholine is accompanied by the expression of acetylcholinesterase and nicotinic/muscarinic acetylcholine receptors. Increasing evidence of the non-neuronal acetylcholine system found throughout the last few years has indicated this neurotransmitter as one of the major cellular signaling molecules (associated e.g. with kinases and transcription factors activity). This system is responsible for maintenance and optimization of the cellular function, such as proliferation, differentiation, adhesion, migration, intercellular contact and apoptosis. Additionally, it controls proper activity of immune cells and affects differentiation, antigen presentation or cytokine production (both pro- and anti-inflammatory). The present article reviews recent findings about the non-neuronal cholinergic system in the field of immune system and intracellular signaling pathways.
REFERENCES (83)
1.
Loewi O (1921): Über humerole übertragbarkeit der herznervenwirkung. I. Mitteilung. Pflügers Arch Ges Physiol 189: 239-242.
2.
Picciotto MR, Higley MJ, Mineur YS (2012): Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron 76: 116-129.
3.
Fagerlund MJ, Eriksson LI (2009): Current concepts in neuromuscular transmission. Br J Anaesth 103: 108-114.
4.
Millar NS (2003): Assembly and subunit diversity of nicotinic acetylcholine receptors. Biochem Soc Trans 31: 869-874.
5.
Albuquerque EX, Pereira EF, Alkondon M, et al. (2009): Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol Rev 89: 73-120.
6.
Sastry BV, Sadavongvivad C (1978): Cholinergic systems in non-nervous tissues. Pharmacol Rev 30: 65-132.
7.
Zia S, Ndoye A, Lee TX, et al. (2000): Receptor-mediated inhibition of keratinocyte migration by nicotine involves modulations of calcium influx and intracellular concentration. J Pharmacol Exp Ther 293: 973-981.
8.
Kawashima K, Yoshikawa K, Fujii YX, et al. (2007): Expression and function of genes encoding cholinergic components in murine immune cells. Life Sci 80: 2314-2319.
9.
Wang Y, Pereira EF, Maus AD, et al. (2001): Human bronchial epithelial and endothelial cells express α7 nicotinic acetylcholine receptors. Mol Pharmacol 60: 1201-1209.
10.
Zia S, Ndoye A, Nguyen VT, et al. (1997): Nicotine enhances expression of the α3, α4, α5 and α7 nicotinic receptors modulating calcium metabolism and regulating adhesion and motility of respiratory epithelial cells. Res Commun Mol Pathol Pharmacol 97: 243-262.
11.
Wessler I, Kirkpatrick CJ, Racke K (1998): Non-neuronal acetylcholine, a locally acting molecule, widely distributed in biological systems: expression and function in humans. Pharmacol Ther 77: 59-79.
12.
Improgo MR, Soll LG, Tapper AR, et al. (2013): Nicotinic acetylcholine receptors mediate lung cancer growth. Front Physiol 4: 251.
13.
Cooke JP, Ghebremariam YT (2008): Endothelial Nicotinic Acetylcholine Receptors and Angiogenesis. Trends Cardiovasc Med 18: 247-253.
14.
de Jonge WJ, Ulloa L (2007): The alpha7 nicotinic acetylcholine receptor as a pharmacologicaltarget for inflammation. Br J Pharmacol 151: 915-929.
15.
Schirmer SU, Eckhardt I, Lau H, et al. (2011): The cholinergic system in rat testis is of non-neuronal origin. Reproduction 142: 157-166.
16.
Davis TJ, de Fiebre CM (2006): Alcohol’s actions on neuronal nicotinic acetylcholine receptors. Alcohol Res Health 29: 179-185.
17.
Reardon C, Duncan GS, Brüstle A, et al. Lymphocyte-derived ACh regulates local innate but not adaptive immunity. Proc Natl Acad Sci U S A 110: 1410-1415.
18.
Matteoli G, Boeckxstaens GE (2013): The vagal innervation of the gut and immune homeostasis. Gut 62: 1214-1222.
19.
Sato KZ, Fujii T, Watanabe Y, et al. (1999): Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines. Neurosci Lett 266: 17-20.
20.
Skok MV, Kalashnik EN, Koval LN, et al. (2003): Functional nicotinic acetylcholine receptors are expressed in B lymphocyte-derived cell lines. Mol Pharmacol 64: 885-889.
21.
Sudheer PS, Hall JE, Donev R, et al. (2006): Nicotinic acetylcholine receptors on basophils and mast cells. Anaesthesia 61: 1170-1174.
22.
Rosas-Ballina M, Ochani M, Parrish WR, et al. (2008): Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proc Natl Acad Sci U S A 105: 11008-11013.
23.
Rosas-Ballina M, Olofsson PS, Ochani M, et al. (2011): Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit. Science 334: 98-101.
25.
α7 nicotinic acetylcholine receptor (α7nAChR) expression in bone marrow-derived non-T cells is required for the inflammatory reflex. Mol Med 18: 539-543.
26.
Parrish WR, Rosas-Ballina M, Gallowitsch-Puerta M, et al. (2008): Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor mediated signaling. Mol Med 14: 567-574.
27.
Sun F, Jin K, Uteshev VV (2013): A type-II positive allosteric modulator of α7 nAChRs reduces brain injury and improves neurological function after focal cerebral ischemia in rats. PLoS One 8: e73581.
28.
Freitas K, Carroll FI, Damaj MI (2013): The antinociceptive effects of nicotinic receptors α7-positive allosteric modulators in murine acute and tonic pain models. J Pharmacol Exp Ther 344: 264-275.
29.
Wang H, Yu M, Ochani M, et al. (2003): Nicotinic acetylcholine receptor _7 subunit is an essential regulator of inflammation. Nature 421: 384-388.
30.
Borovikova LV, Ivanova S, Zhang M, et al. (2000): Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405: 458-462.
31.
Rosas-Ballina M, Goldstein RS, Gallowitsch-Puerta M, et al. (2009): The selective alpha7 agonist GTS-21 attenuates cytokine production in human whole blood and human monocytes activated by ligands for TLR2, TLR3, TLR4, TLR9, and RAGE. Mol Med 15: 195-202.
32.
Shytle RD, Mori T, Townsend K (2004): Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors. J Neurochem 89: 337-343.
33.
Kawashima K, Fujii T (2000): Extraneuronal cholinergic system in lymphocytes. Pharmacol Ther 86: 29-48.
34.
Kawashima K, Fujii T (2003): The lymphocytic cholinergic system and its contribution to the regulation of immune activity. Life Sci 74: 675-696.
35.
Kawashima K, Fujii T (2004): Expression of non-neuronal acetylcholine in lymphocytes and its contribution to the regulation of immune function. Front Biosci 9: 2063-2685.
36.
Fujii T, Tsuchiya T, Yamada S, et al. (1996): Localization and synthesis of acetylcholine in human leukemic T cell lines. J Neurosci Res 44: 66-72.
37.
Wang DW, Zhou RB, Yao YM, et al. (2010): Stimulation of α7 nicotinic acetylcholine receptor by nicotine increases suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro. J Pharmacol Exp Ther 335: 553-561.
38.
Nordman JC, Muldoon P, Clark S, et al. (2014): The α4 nicotinic receptor promotes CD4+ T-cell proliferation and a helper T-cell immune response. Mol Pharmacol 85: 50-61.
39.
Nouri-Shirazi M, Tinajero R, Guinet E (2007): Nicotine alters the biological activities of developing mouse bone marrow-derived dendritic cells (Dcs). Immunol Lett 109: 155-164.
40.
Vassallo R, Tamada K, Lau JS, (2005): Cigarette smoke extract suppresses human dendritic cell function leading to preferential induction of Th-2 priming. J Immunol 175: 2684-2691.
41.
Nouri-Shirazi M, Guinet E (2012): Exposure to nicotine adversely affects the dendritic cell system and compromises host response to vaccination. J Immunol 188: 2359-2370.
42.
Radosa J, Dyck W, Goerdt S, et al. (2011): The cholinergic system in guttate psoriasis with special reference to mast cells. Exp Dermatol 20: 677-679.
43.
Mishra NC, Rir-Sima-Ah J, Boyd RT, et al. (2010): Nicotine inhibits fc RI-induced cysteinyl leukotrienes and cytokine production without affecting mast cell degranulation through alpha7/alpha9/alpha10-nicotinic receptors. J Immunol 185: 588-596.
44.
Kageyama-Yahara N, Suehiro Y, Yamamoto T, et al. (2009): IgE-induced degranulation of mucosal mast cells is negatively regulated via nicotinic acetylcholine receptors. Biochem Biophys Res Commun 377: 321-325.
45.
Huston JM, Rosas-Ballina M, Xue X, et al. (2009): Cholinergic neural signals to the spleen down-regulate leukocyte trafficking via CD11b. J Immunol 183: 552-559.
46.
Gilboa-Geffen A, Lacoste PP, Soreq L, et al. (2007): The thymic theme of acetylcholinesterase splice variants in myasthenia gravis. Blood 109: 4383-4391.
47.
Gilboa-Geffen A, Wolf Y, Hanin G, et al. (2011): Activation of the alternative NFB pathway improves disease symptoms in a model of Sjogren’s syndrome. PLoS One 6: e28727.
48.
Ofek K, Krabbe KS, Evron T, et al. (2007): Cholinergic status modulations in human volunteers under acute inflammation. J Mol Med (Berl) 85: 1239-1251.
49.
Brenner T, Hamra-Amitay Y, Evron T, et al. (2003): The role of readthrough acetylcholinesterase in the pathophysiology of myasthenia gravis. FASEB J 17: 214-222.
50.
Nadorp B, Soreq H (2014): Predicted overlapping microRNA regulators of acetylcholine packaging and degradation in neuroinflammation-related disorders. Front Mol Neurosci 7: 9, doi: 10.3389/fnmol.2014.00009. eCollection 2014.
51.
Perry C, Pick M, Podoly E, et al. (2007): Acetylcholinesterase/C terminal binding protein interactions modify Ikaros functions, causing T lymphopenia. Leukemia 21: 1472-1480.
52.
Couturier S, Bertrand D, Matter JM, et al. (1990): A neuronal nicotinic acetylcholine receptor subunit (alpha7) is developmentally regulated and forms a homooligomeric channel blocked by alpha-BTX. Neuron 5: 847-856.
53.
Smedlund K, Tano JY, Margiotta J, et al. (2011): Evidence for operation of nicotinic and muscarinic acetylcholine receptor-dependent survival pathways in human coronary artery endothelial cells. J Cell Biochem 112: 1978-1984.
54.
Schuller HM, Plummer HK 3rd, Jull BA (2003): Receptor-mediated effects of nicotine and its nitrosated derivative NNK on pulmonary neuroendocrine cells. Anat Rec A Discov Mol Cell Evol Biol 270: 51-58.
55.
Jull BA, Plummer HK 3rd, Schuller HM (2001): Nicotinic receptor-mediated activation by the tobacco-specific nitrosamine NNK of a Raf-1/MAP kinase pathway, resulting in phosphorylation of c-myc in human small cell lung carcinoma cells and pulmonary neuroendocrine cells. J Cancer Res Clin Oncol 127: 707-717.
56.
Paulo JA, Brucker WJ, Hawrot E (2009): Proteomic analysis of an α7 nicotinic acetylcholine receptor interactome. J Proteome Res 8: 1849-1858.
57.
Marrero MB, Bencherif M (2009): Convergence of alpha 7 nicotinic acetylcholine receptor-activated pathways for anti-apoptosis and anti-inflammation: central role for JAK2 activation of STAT3 and NF-kappaB. Brain Res 1256: 1-7.
58.
Tsurutani J, Castillo SS, Brognard J, et al. (2005): Tobacco components stimulate Akt-dependent proliferation and NFB dependent survival in lung cancer cells. Carcinogenesis 26: 1182-1195.
59.
de Jonge WJ, van der Zanden EP, The FO, et al. (2005): Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 6: 844-851.
60.
Chernyavsky AI, Arredondo J, Karlsson E, et al. (2005): The Ras/Raf-1/MEK1/ERK signaling pathway coupled to integrin expression mediates cholinergic regulation of keratinocyte directional migration. J Biol Chem 280: 39220-39228.
61.
Trombino S, Cesario A, Margaritora S, et al. (2004): α7-nicotinic acetylcholine receptors affect growth regulation of human mesothelioma cells: role of mitogen-activated protein kinase pathway. Cancer Res 64: 135-145.
62.
Paleari L, Catassi A, Ciarlo M, et al. (2008): Role of alpha7-nicotinic acetylcholine receptor in human non-small cell lung cancer proliferation. Cell Prolif 41: 936-959.
63.
Wang H, Liao H, Ochani M, et al. (2004): Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 10: 1216-1221.
64.
Terrando N, Eriksson LI, Ryu JK, et al. (2011): Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol 70: 986-995.
65.
Waldburger JM, Boyle DL, Pavlov VA, et al. (2008): Acetylcholine regulation of synoviocyte cytokine expression by the alpha7 nicotinic receptor. Arthritis Rheum 58: 3439-3449.
66.
Al-Wadei MH, Al-Wadei HA, Schuller HM (2012): Pancreatic cancer cells and normal pancreatic duct epithelial cells express an autocrine catecholamine loop that is activated by nicotinic acetylcholine receptors α3, α5, and α7. Mol Cancer Res 10: 239-249.
67.
Nakamura S, Saitoh M, Yamazaki M, et al. (2010): Nicotine induces upregulated expression of beta defensin-2 via the p38MAPK pathway in the HaCaT human keratinocyte cell line. Med Mol Morphol 43: 204-210.
68.
Li Q, Zhou XD, Kolosov VP, et al. (2011): Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-B pathway in HBE16 airway epithelial cells. Cell Physiol Biochem 27: 605-612.
69.
Carlisle DL, Hopkins TM, Gaither-Davis A, et al. (2004): Nicotine signals through muscle-type and neuronal nicotinic acetylcholine receptors in both human bronchial epithelial cells and airway fibroblasts. Respir Res 5: 27, doi: 10.1186/1465-9921-5-27.
70.
West KA, Brognard J, Clark AS, et al. (2003): Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. J Clin Invest 111: 81-90.
71.
Novak J, Escobedo-Morse A, Kelley K, et al. (2000): Nicotine effects on proliferation and the bombesin-like peptide autocrine system in human small cell lung carcinoma SHP77 cells in culture. Lung Cancer 29: 1-10.
72.
Lawlor MA, Alessi DR (2001): PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J Cell Sci 114: 2903-2910.
73.
Xin M, Deng X (2005): Nicotine inactivation of the proapoptotic function of Bax through phosphorylation. J Biol Chem 280: 10781-10789.
74.
Scheid MP, Woodgett JR (2001): Pkb/akt: functional insights from genetic models. Nat Rev Mol Cell Biol 2: 760-768.
75.
Kihara T, Shimohama S, Sawada H, et al. (2001): Alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity. J Biol Chem 276: 13541-13546.
76.
Carlisle DL, Liu X, Hopkins TM, et al. (2007): Nicotine activates cell-signaling pathways through muscle-type and neuronal nicotinic acetylcholine receptors in non-small cell lung cancer cells. Pulm Pharmacol Ther 20: 629-641.
77.
Ueno H, Pradhan S, Schlessel D, et al. (2006): Nicotine enhances human vascular endothelial cell expression of ICAM-1 and VCAM-1 via protein kinase C, p38 mitogen-activated protein kinase, NF-kappaB, and AP-1. Cardiovasc Toxicol 6: 39-50.
78.
Chatterjee PK, Al-Abed Y, Sherry B, et al. (2009): Cholinergic agonists regulate JAK2/STAT3 signaling to suppress endothelial cell activation. Am J Physiol Cell Physiol 297: C1294-C12306.
79.
Saeed RW, Varma S, Peng-Nemeroff T, et al. (2005): Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med 201: 1113-1123.
80.
Chen RJ, Ho YS, Guo HR, et al. (2008): Rapid activation of Stat3 and ERK1/2 by nicotine modulates cell proliferation in human bladder cancer cells. Toxicol Sci 104: 283-293.
81.
Chen RJ, Ho YS, Guo HR, et al. (2010): Long-term nicotine exposure-induced chemoresistance is mediated by activation of Stat3 and downregulation of ERK1/2 via nAChR and beta-adrenoceptors in human bladder cancer cells. Toxicol Sci 115: 118-130.
82.
Zeidler R, Albermann K, Lang S (2007): Nicotine and apoptosis. Apoptosis 12: 1927-1943.
83.
Jin Z, Gao F, Flagg T, et al. (2004): Nicotine induces multi-site phosphorylation of Bad in association with suppression of apoptosis. J Biol Chem 279: 23837-23844. .
Share
RELATED ARTICLE
| eISSN: | 1644-4124 |
| ISSN: | 1426-3912 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
