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Nicotinic Modulation of Innate Immune Pathways Via α7 Nicotinic Acetylcholine Receptor

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An Erratum to this article was published on 05 June 2010

Abstract

The major addictive component of tobacco, nicotine, exerts anti-inflammatory effects in multiple cell types and may benefit neurons in various degenerative disorders, such as Alzheimer’s and Parkinson’s disease, in which an inflammation-related mechanism is implicated. Among the various nicotinic acetylcholine receptors, α7, which has been identified in both neurons and immune cells and has high permeability to calcium, is believed to contribute significantly to nicotinic anti-inflammatory and neuron-protective effects. Although nicotine has been used in clinical trials for the treatment of some inflammatory diseases such as ulcerative colitis, the molecular mechanisms of its actions are largely unknown. In this review, we provide current evidence for nicotine’s modulation of multiple immune pathways via α7 nAChRs in both neurons and immune cells. Understanding the mechanism of the nicotinic anti-inflammatory effect and neuron-protective function may guide the development of novel medicines for infectious and neuron-degenerative diseases.

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References

  • Aicher A, Heeschen C, Mohaupt M, Cooke JP, Zeiher AM, Dimmeler S (2003) Nicotine strongly activates dendritic cell-mediated adaptive immunity: potential role for progression of atherosclerotic lesions. Circulation 107:604–611

    Article  PubMed  CAS  Google Scholar 

  • Albuquerque EX, Pereira EF, Castro NG, Alkondon M, Reinhardt S, Schroder H, Maelicke A (1995) Nicotinic receptor function in the mammalian central nervous system. Ann N Y Acad Sci 757:48–72

    Article  PubMed  CAS  Google Scholar 

  • Albuquerque EX, Pereira EF, Alkondon M, Rogers SW (2009) Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol Rev 89:73–120

    Article  PubMed  CAS  Google Scholar 

  • Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson-Harris H, Janson A, Kokkola R, Zhang M, Yang H, Tracey KJ (2000) High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med 192:565–570

    Article  PubMed  CAS  Google Scholar 

  • Baeuerle PA, Henkel T (1994) Function and activation of NF-kappa B in the immune system. Annu Rev Immunol 12:141–179

    PubMed  CAS  Google Scholar 

  • Barnes PJ (2003) New concepts in chronic obstructive pulmonary disease. Annu Rev Med 54:113–129

    Article  PubMed  CAS  Google Scholar 

  • Barr RS, Culhane MA, Jubelt LE, Mufti RS, Dyer MA, Weiss AP, Deckersbach T, Kelly JF, Freudenreich O, Goff DC, Evins AE (2008) The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology 33:480–490

    Article  PubMed  CAS  Google Scholar 

  • Benveniste EN (1997) Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med 75:165–173

    Article  PubMed  CAS  Google Scholar 

  • Berg DK, Conroy WG (2002) Nicotinic alpha 7 receptors: synaptic options and downstream signaling in neurons. J Neurobiol 53:512–523

    Article  PubMed  CAS  Google Scholar 

  • Beutler B (2002) Toll-like receptors: how they work and what they do. Curr Opin Hematol 9:2–10

    Article  PubMed  Google Scholar 

  • Beutler B (2003a) Innate immune responses to microbial poisons: discovery and function of the Toll-like receptors. Annu Rev Pharmacol Toxicol 43:609–628

    Article  PubMed  CAS  Google Scholar 

  • Beutler B (2003b) Science review: key inflammatory and stress pathways in critical illness—the central role of the Toll-like receptors. Crit Care 7:39–46

    Article  PubMed  Google Scholar 

  • Blanchet MR, Israel-Assayag E, Daleau P, Beaulieu MJ, Cormier Y (2006) Dimethyphenylpiperazinium, a nicotinic receptor agonist, downregulates inflammation in monocytes/macrophages through PI3K and PLC chronic activation. Am J Physiol Lung Cell Mol Physiol 291:L757–L763

    Article  PubMed  CAS  Google Scholar 

  • Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462

    Article  PubMed  CAS  Google Scholar 

  • Bustin M (2002) At the crossroads of necrosis and apoptosis: signaling to multiple cellular targets by HMGB1. Sci STKE 2002, pe39

  • CDC (1997) Annual smoking-attributable mortality and years of potential life lost—United States, 1984. MMWR Morb Mortal Wkly Rep 46:444–451

    Google Scholar 

  • CDC (2002) Annual smoking-attributable mortality, years of potential life lost, and economic costs—United States, 1995–1999. MMWR Morb Mortal Wkly Rep 51:300–303

    Google Scholar 

  • CDC (2005) Annual smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 1997–2001. MMWR Morb Mortal Wkly Rep 54:625–628

    Google Scholar 

  • CDC (2007) Cigarette smoking among adults—United States, 2006. MMWR Morb Mortal Wkly Rep 56:1157–1161

    Google Scholar 

  • Charpantier E, Wiesner A, Huh KH, Ogier R, Hoda JC, Allaman G, Raggenbass M, Feuerbach D, Bertrand D, Fuhrer C (2005) Alpha7 neuronal nicotinic acetylcholine receptors are negatively regulated by tyrosine phosphorylation and Src-family kinases. J Neurosci 25:9836–9849

    Article  PubMed  CAS  Google Scholar 

  • Colquhoun D (1987) Molecular neurobiology. A new type of ion-channel block. Nature 329:204–205

    Article  PubMed  CAS  Google Scholar 

  • D'Hoedt D, Bertrand D (2009) Nicotinic acetylcholine receptors: an overview on drug discovery. Expert Opin Ther Targets 13:395–411

    Article  PubMed  Google Scholar 

  • Dajas-Bailador FA, Soliakov L, Wonnacott S (2002) Nicotine activates the extracellular signal-regulated kinase 1/2 via the alpha7 nicotinic acetylcholine receptor and protein kinase A, in SH-SY5Y cells and hippocampal neurones. J Neurochem 80:520–530

    Article  PubMed  CAS  Google Scholar 

  • Dalack GW, Healy DJ, Meador-Woodruff JH (1998) Nicotine dependence in schizophrenia: clinical phenomena and laboratory findings. Am J Psychiatry 155:1490–1501

    PubMed  CAS  Google Scholar 

  • Damaj MI (2000) The involvement of spinal Ca(2+)/calmodulin-protein kinase II in nicotine-induced antinociception in mice. Eur J Pharmacol 404:103–110

    Article  PubMed  CAS  Google Scholar 

  • de Jonge WJ, Ulloa L (2007) The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol 151:915–929

    Article  PubMed  CAS  Google Scholar 

  • de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ, Berthoud HR, Uematsu S, Akira S, van den Wijngaard RM, Boeckxstaens GE (2005) Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 6:844–851

    Article  PubMed  CAS  Google Scholar 

  • Derkach VA, Selyanko AA, Skok VI (1983) Acetylcholine-induced current fluctuations and fast excitatory post-synaptic currents in rabbit sympathetic neurones. J Physiol 336:511–526

    PubMed  CAS  Google Scholar 

  • Drisdel RC, Green WN (2000) Neuronal alpha-bungarotoxin receptors are alpha7 subunit homomers. J Neurosci 20:133–139

    PubMed  CAS  Google Scholar 

  • Dunckley T, Lukas RJ (2003) Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. J Biol Chem 278:15633–15640

    Article  PubMed  CAS  Google Scholar 

  • Dunckley T, Lukas RJ (2006) Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res 1116:39–49

    Article  PubMed  CAS  Google Scholar 

  • Ferrari S, Ronfani L, Calogero S, Bianchi ME (1994) The mouse gene coding for high mobility group 1 protein (HMG1). J Biol Chem 269:28803–28808

    PubMed  CAS  Google Scholar 

  • Flores CM, DeCamp RM, Kilo S, Rogers SW, Hargreaves KM (1996) Neuronal nicotinic receptor expression in sensory neurons of the rat trigeminal ganglion: demonstration of alpha3beta4, a novel subtype in the mammalian nervous system. J Neurosci 16:7892–7901

    PubMed  CAS  Google Scholar 

  • Fujii T, Takada-Takatori Y, Kawashima K (2008) Basic and clinical aspects of non-neuronal acetylcholine: expression of an independent, non-neuronal cholinergic system in lymphocytes and its clinical significance in immunotherapy. J Pharmacol Sci 106:186–192

    Article  PubMed  CAS  Google Scholar 

  • Fujii YX, Fujigaya H, Moriwaki Y, Misawa H, Kasahara T, Grando SA, Kawashima K (2007) Enhanced serum antigen-specific IgG1 and proinflammatory cytokine production in nicotinic acetylcholine receptor alpha7 subunit gene knockout mice. J Neuroimmunol 189:69–74

    Article  PubMed  CAS  Google Scholar 

  • Galvis G, Lips KS, Kummer W (2006) Expression of nicotinic acetylcholine receptors on murine alveolar macrophages. J Mol Neurosci 30:107–108

    Article  PubMed  CAS  Google Scholar 

  • Gehrmann J, Matsumoto Y, Kreutzberg GW (1995) Microglia: intrinsic immuneffector cell of the brain. Brain Res Brain Res Rev 20:269–287

    Article  PubMed  CAS  Google Scholar 

  • Glassman AH (1993) Cigarette smoking: implications for psychiatric illness. Am J Psychiatry 150:546–553

    PubMed  CAS  Google Scholar 

  • Gotti C, Clementi F (2004) Neuronal nicotinic receptors: from structure to pathology. Prog Neurobiol 74:363–396

    Article  PubMed  CAS  Google Scholar 

  • Guarini S, Altavilla D, Cainazzo MM, Giuliani D, Bigiani A, Marini H, Squadrito G, Minutoli L, Bertolini A, Marini R, Adamo EB, Venuti FS, Squadrito F (2003) Efferent vagal fibre stimulation blunts nuclear factor-kappaB activation and protects against hypovolemic hemorrhagic shock. Circulation 107:1189–1194

    Article  PubMed  Google Scholar 

  • Guinet E, Yoshida K, Nouri-Shirazi M (2004) Nicotinic environment affects the differentiation and functional maturation of monocytes derived dendritic cells (DCs). Immunol Lett 95:45–55

    Article  PubMed  CAS  Google Scholar 

  • Gutala R, Wang J, Hwang YY, Haq R, Li MD (2006) Nicotine modulates expression of amyloid precursor protein and amyloid precursor-like protein 2 in mouse brain and in SH-SY5Y neuroblastoma cells. Brain Res 1093:12–19

    Article  PubMed  CAS  Google Scholar 

  • Hamano R, Takahashi HK, Iwagaki H, Yoshino T, Nishibori M, Tanaka N (2006) Stimulation of alpha7 nicotinic acetylcholine receptor inhibits CD14 and the toll-like receptor 4 expression in human monocytes. Shock 26:358–364

    Article  PubMed  CAS  Google Scholar 

  • Hecker A, Mikulski Z, Lips KS, Pfeil U, Zakrzewicz A, Wilker S, Hartmann P, Padberg W, Wessler I, Kummer W, Grau V (2009) Pivotal advance: up-regulation of acetylcholine synthesis and paracrine cholinergic signaling in intravascular transplant leukocytes during rejection of rat renal allografts. J Leukoc Biol 86:13–22

    Article  PubMed  CAS  Google Scholar 

  • Hejmadi MV, Dajas-Bailador F, Barns SM, Jones B, Wonnacott S (2003) Neuroprotection by nicotine against hypoxia-induced apoptosis in cortical cultures involves activation of multiple nicotinic acetylcholine receptor subtypes. Mol Cell Neurosci 24:779–786

    Article  PubMed  CAS  Google Scholar 

  • Hellstrom-Lindahl E, Court J, Keverne J, Svedberg M, Lee M, Marutle A, Thomas A, Perry E, Bednar I, Nordberg A (2004) Nicotine reduces A beta in the brain and cerebral vessels of APPsw mice. Eur J NeuroSci 19:2703–2710

    Article  PubMed  Google Scholar 

  • Hoebe K, Du X, Georgel P, Janssen E, Tabeta K, Kim SO, Goode J, Lin P, Mann N, Mudd S, Crozat K, Sovath S, Han J, Beutler B (2003) Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424:743–748

    Article  PubMed  CAS  Google Scholar 

  • Kalamida D, Poulas K, Avramopoulou V, Fostieri E, Lagoumintzis G, Lazaridis K, Sideri A, Zouridakis M, Tzartos SJ (2007) Muscle and neuronal nicotinic acetylcholine receptors. Structure, function and pathogenicity. Febs J 274:3799–3845

    Article  PubMed  CAS  Google Scholar 

  • Kihara T, Shimohama S, Sawada H, Kimura J, Kume T, Kochiyama H, Maeda T, Akaike A (1997) Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity. Ann Neurol 42:159–163

    Article  PubMed  CAS  Google Scholar 

  • Kihara T, Shimohama S, Sawada H, Honda K, Nakamizo T, Shibasaki H, Kume T, Akaike A (2001) Alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity. J Biol Chem 276:13541–13546

    PubMed  CAS  Google Scholar 

  • Kincade JE, Dougherty MC, Busby-Whitehead J, Carlson JR, Nix WB, Kelsey DT, Smith FC, Hunter GS, Rix AD (2005) Self-monitoring and pelvic floor muscle exercises to treat urinary incontinence. Urol Nurs 25:353–363

    PubMed  Google Scholar 

  • Kreutzberg GW (1995) Microglia, the first line of defence in brain pathologies. Arzneimittelforschung 45:357–360

    PubMed  CAS  Google Scholar 

  • Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318

    Article  PubMed  CAS  Google Scholar 

  • Kumari V, Gray JA, Ffytche DH, Mitterschiffthaler MT, Das M, Zachariah E, Vythelingum GN, Williams SC, Simmons A, Sharma T (2003) Cognitive effects of nicotine in humans: an fMRI study. Neuroimage 19:1002–1013

    Article  PubMed  Google Scholar 

  • Langley JN (1905) On the reaction of cells and of nerve-endings to certain poisons, chiefly as regards the reaction of striated muscle to nicotine and to curari. J Physiol 33:374–413

    PubMed  Google Scholar 

  • Lau PP, Li L, Merched AJ, Zhang AL, Ko KW, Chan L (2006) Nicotine induces proinflammatory responses in macrophages and the aorta leading to acceleration of atherosclerosis in low-density lipoprotein receptor(-/-) mice. Arterioscler Thromb Vasc Biol 26:143–149

    Article  PubMed  CAS  Google Scholar 

  • Li J, Kokkola R, Tabibzadeh S, Yang R, Ochani M, Qiang X, Harris HE, Czura CJ, Wang H, Ulloa L, Wang H, Warren HS, Moldawer LL, Fink MP, Andersson U, Tracey KJ, Yang H (2003) Structural basis for the proinflammatory cytokine activity of high mobility group box 1. Mol Med 9:37–45

    PubMed  CAS  Google Scholar 

  • Li Q, Verma IM (2002) NF-kappaB regulation in the immune system. Nat Rev Immunol 2:725–734

    Article  PubMed  CAS  Google Scholar 

  • Liu Q, Kawai H, Berg DK (2001) Beta-amyloid peptide blocks the response of alpha 7-containing nicotinic receptors on hippocampal neurons. Proc Natl Acad Sci U S A 98:4734–4739

    Article  PubMed  CAS  Google Scholar 

  • Liu Q, Zhang J, Zhu H, Qin C, Chen Q, Zhao B (2007) Dissecting the signaling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer disease model. Faseb J 21:61–73

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Yao M, Li N, Wang C, Zheng Y, Cao X (2008) CaMKII promotes TLR-triggered proinflammatory cytokine and type I interferon production by directly binding and activating TAK1 and IRF3 in macrophages. Blood 112:4961–4970

    Article  PubMed  CAS  Google Scholar 

  • McCallum SE, Collins AC, Paylor R, Marks MJ (2006) Deletion of the beta 2 nicotinic acetylcholine receptor subunit alters development of tolerance to nicotine and eliminates receptor upregulation. Psychopharmacology (Berl) 184:314–327

    Article  CAS  Google Scholar 

  • Messing RO, Stevens AM, Kiyasu E, Sneade AB (1989) Nicotinic and muscarinic agonists stimulate rapid protein kinase C translocation in PC12 cells. J Neurosci 9:507–512

    PubMed  CAS  Google Scholar 

  • Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318

    Article  PubMed  CAS  Google Scholar 

  • Nordberg A, Hellstrom-Lindahl E, Lee M, Johnson M, Mousavi M, Hall R, Perry E, Bednar I, Court J (2002) Chronic nicotine treatment reduces beta-amyloidosis in the brain of a mouse model of Alzheimer's disease (APPsw). J Neurochem 81:655–658

    Article  PubMed  CAS  Google Scholar 

  • Nouri-Shirazi M, Guinet E (2003) Evidence for the immunosuppressive role of nicotine on human dendritic cell functions. Immunology 109:365–373

    Article  PubMed  CAS  Google Scholar 

  • Nuorti JP, Butler JC, Farley MM, Harrison LH, McGeer A, Kolczak MS, Breiman RF (2000) Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team. N Engl J Med 342:681–689

    Article  PubMed  CAS  Google Scholar 

  • Orr-Urtreger A, Kedmi M, Rosner S, Karmeli F, Rachmilewitz D (2005) Increased severity of experimental colitis in alpha 5 nicotinic acetylcholine receptor subunit-deficient mice. NeuroReport 16:1123–1127

    Article  PubMed  CAS  Google Scholar 

  • Paonessa G, Frank R, Cortese R (1987) Nucleotide sequence of rat liver HMG1 cDNA. Nucleic Acids Res 15:9077

    Article  PubMed  CAS  Google Scholar 

  • Pavlov VA, Ochani M, Yang LH, Gallowitsch-Puerta M, Ochani K, Lin X, Levi J, Parrish WR, Rosas-Ballina M, Czura CJ, Larosa GJ, Miller EJ, Tracey KJ, Al-Abed Y (2007) Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med 35:1139–1144

    Article  PubMed  CAS  Google Scholar 

  • Picciotto MR, Zoli M (2002) Nicotinic receptors in aging and dementia. J Neurobiol 53:641–655

    Article  PubMed  CAS  Google Scholar 

  • Pullan RD, Rhodes J, Ganesh S, Mani V, Morris JS, Williams GT, Newcombe RG, Russell MA, Feyerabend C, Thomas GA et al (1994) Transdermal nicotine for active ulcerative colitis. N Engl J Med 330:811–815

    Article  PubMed  CAS  Google Scholar 

  • Rangwala F, Drisdel RC, Rakhilin S, Ko E, Atluri P, Harkins AB, Fox AP, Salman SS, Green WN (1997) Neuronal alpha-bungarotoxin receptors differ structurally from other nicotinic acetylcholine receptors. J Neurosci 17:8201–8212

    PubMed  CAS  Google Scholar 

  • Razani-Boroujerdi S, Boyd RT, Davila-Garcia MI, Nandi JS, Mishra NC, Singh SP, Pena-Philippides JC, Langley R, Sopori ML (2007) T cells express alpha7-nicotinic acetylcholine receptor subunits that require a functional TCR and leukocyte-specific protein tyrosine kinase for nicotine-induced Ca2+ response. J Immunol 179:2889–2898

    PubMed  CAS  Google Scholar 

  • Rezvani AH, Levin ED (2001) Cognitive effects of nicotine. Biol Psychiatry 49:258–267

    Article  PubMed  CAS  Google Scholar 

  • Rubin DT, Hanauer SB (2000) Smoking and inflammatory bowel disease. Eur J Gastroenterol Hepatol 12:855–862

    Article  PubMed  CAS  Google Scholar 

  • Saeed RW, Varma S, Peng-Nemeroff T, Sherry B, Balakhaneh D, Huston J, Tracey KJ, Al-Abed Y, Metz CN (2005) Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med 201:1113–1123

    Article  PubMed  CAS  Google Scholar 

  • Sahakian B, Jones G, Levy R, Gray J, Warburton D (1989) The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Br J Psychiatry 154:797–800

    Article  PubMed  CAS  Google Scholar 

  • Sahakian BJ, Coull JT (1994) Nicotine and tetrahydroaminoacradine—evidence for improved attention in patients with dementia of the Alzheimer-type. Drug Dev Res 31:80–88

    Article  Google Scholar 

  • Shaw S, Bencherif M, Marrero MB (2002) Janus kinase 2, an early target of alpha 7 nicotinic acetylcholine receptor-mediated neuroprotection against Abeta-(1-42) amyloid. J Biol Chem 277:44920–44924

    Article  PubMed  CAS  Google Scholar 

  • Shi FD, Piao WH, Kuo YP, Campagnolo DI, Vollmer TL, Lukas RJ (2009) Nicotinic attenuation of central nervous system inflammation and autoimmunity. J Immunol 182:1730–1739

    Article  PubMed  CAS  Google Scholar 

  • Shytle RD, Mori T, Townsend K, Vendrame M, Sun N, Zeng J, Ehrhart J, Silver AA, Sanberg PR, Tan J (2004) Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors. J Neurochem 89:337–343

    Article  PubMed  CAS  Google Scholar 

  • Siegel PZ, Huston SL, Powell KE, Baptiste MS, Tilson HH, Jacobellis J, Brownson RC (2007) Assessment of chronic disease epidemiology workforce in state health departments—United States, 2003. Prev Chronic Dis 4:A76

    PubMed  Google Scholar 

  • Skok M, Grailhe R, Agenes F, Changeux JP (2006) The role of nicotinic acetylcholine receptors in lymphocyte development. J Neuroimmunol 171:86–98

    Article  PubMed  CAS  Google Scholar 

  • Streit WJ (2002) Microglia as neuroprotective, immunocompetent cells of the CNS. Glia 40:133–139

    Article  PubMed  Google Scholar 

  • Sugano N, Shimada K, Ito K, Murai S (1998) Nicotine inhibits the production of inflammatory mediators in U937 cells through modulation of nuclear factor-kappaB activation. Biochem Biophys Res Commun 252:25–28

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T, Hide I, Matsubara A, Hama C, Harada K, Miyano K, Andra M, Matsubayashi H, Sakai N, Kohsaka S, Inoue K, Nakata Y (2006) Microglial alpha7 nicotinic acetylcholine receptors drive a phospholipase C/IP3 pathway and modulate the cell activation toward a neuroprotective role. J Neurosci Res 83:1461–1470

    Article  PubMed  CAS  Google Scholar 

  • Takeda K, Clausen BE, Kaisho T, Tsujimura T, Terada N, Forster I, Akira S (1999) Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10:39–49

    Article  PubMed  CAS  Google Scholar 

  • Thomas GA, Rhodes J, Ingram JR (2005) Mechanisms of disease: nicotine—a review of its actions in the context of gastrointestinal disease. Nat Clin Pract Gastroenterol Hepatol 2:536–544

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A, Tracey KJ (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Wang H, Metz C, Miller EJ, Tracey KJ, Ulloa L (2004) Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 10:1216–1221

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421:384–388

    Article  PubMed  CAS  Google Scholar 

  • Wang HY, Lee DH, D'Andrea MR, Peterson PA, Shank RP, Reitz AB (2000a) Beta-amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology. J Biol Chem 275:5626–5632

    Article  PubMed  CAS  Google Scholar 

  • Wang HY, Lee DH, Davis CB, Shank RP (2000b) Amyloid peptide Abeta(1-42) binds selectively and with picomolar affinity to alpha7 nicotinic acetylcholine receptors. J Neurochem 75:1155–1161

    Article  PubMed  CAS  Google Scholar 

  • Welte T, Zhang SS, Wang T, Zhang Z, Hesslein DG, Yin Z, Kano A, Iwamoto Y, Li E, Craft JE, Bothwell AL, Fikrig E, Koni PA, Flavell RA, Fu XY (2003) STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity. Proc Natl Acad Sci U S A 100:1879–1884

    Article  PubMed  CAS  Google Scholar 

  • Wen L, Huang JK, Johnson BH, Reeck GR (1989) A human placental cDNA clone that encodes nonhistone chromosomal protein HMG-1. Nucleic Acids Res 17:1197–1214

    Article  PubMed  CAS  Google Scholar 

  • Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris HE, Susarla SM, Ulloa L, Wang H, DiRaimo R, Czura CJ, Wang H, Roth J, Warren HS, Fink MP, Fenton MJ, Andersson U, Tracey KJ (2004) Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci U S A 101:296–301

    Article  PubMed  CAS  Google Scholar 

  • Yoshikawa H, Kurokawa M, Ozaki N, Nara K, Atou K, Takada E, Kamochi H, Suzuki N (2006) Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7. Clin Exp Immunol 146:116–123

    Article  PubMed  CAS  Google Scholar 

  • Zhou L, Wang X, Wang YJ, Zhou Y, Hu S, Ye L, Hou W, Li H, Ho WZ (2009) Activation of toll-like receptor-3 induces interferon-lambda expression in human neuronal cells. Neuroscience 159:629–637

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

The preparation of this review article was supported in part by NIH grants DA-013783 and DA-026356. The authors thank Dr. David L. Bronson for his excellent editing of this manuscript.

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  1. Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 1670 Discovery Drive, Suite 110, Charlottesville, VA, 22911, USA

    Wen-Yan Cui & Ming D. Li

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  1. Wen-Yan Cui
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Correspondence to Ming D. Li.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s11481-010-9224-9

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Cui, WY., Li, M.D. Nicotinic Modulation of Innate Immune Pathways Via α7 Nicotinic Acetylcholine Receptor. J Neuroimmune Pharmacol 5, 479–488 (2010). https://doi.org/10.1007/s11481-010-9210-2

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