title: Evidence for a prosurvival role of alpha-7 nicotinic acetylcholine receptor in alternatively (M2)-activated macrophages.
abstract: Recent observations in endothelial cells and macrophages indicate that nicotinic acetylcholine receptors (nAChRs) are potential novel players in mechanisms linked to atherogenesis. In macrophages, α7nAChR mediates anti-inflammatory actions and contributes to regulation of cholesterol flux and phagocytosis. Considering that macrophage apoptosis is a key process throughout all stages of atherosclerotic lesion development, in the present study, we examined for the first time the impact of α7nAChR expression and function in macrophage survival and apoptosis using in vitro polarized (M1 and M2) bone marrow-derived macrophages (BMDMs) from wild-type and α7nAChR knockout mice. Our findings show that stimulation of α7nAChR results in activation of the STAT3 prosurvival pathway and protection of macrophages from endoplasmic reticulum (ER) stress-induced apoptosis. These actions are rather selective for M2 BMDMs and are associated to activation of the JAK2/STAT3 axis. Remarkably, these effects are completely lost in M2 macrophages lacking α7nAChR.
authors.affiliation: Department of Physiology and Pharmacology, Center for Diabetes and Endocrine Research, University of Toledo College of Medicine, Health Science Campus, 3000 Arlington Av, Toledo, 43614, Ohio, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lee
authors.affiliation: Department of Physiology and Pharmacology, Center for Diabetes and Endocrine Research, University of Toledo College of Medicine, Health Science Campus, 3000 Arlington Av, Toledo, 43614, Ohio, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Vazquez
keywords: Macrophage polarization; macrophage survival; α7 nicotinic acetylcholine receptor
references.citation: Am J Pathol. 2013 May;182(5):1910-21
references.pmid: 23597852
references.citation: Am J Respir Cell Mol Biol. 2007 Aug;37(2):186-92
references.pmid: 17431097
references.citation: Channels (Austin). 2012 May-Jun;6(3):141-8
references.pmid: 22909953
references.citation: J Neuroinflammation. 2005 Jan 25;2(1):4
references.pmid: 15670336
references.citation: Br J Pharmacol. 2007 Aug;151(7):915-29
references.pmid: 17502850
references.citation: Life Sci. 2009 Sep 9;85(11-12):444-9
references.pmid: 19632243
references.citation: Nat Rev Immunol. 2010 Jan;10(1):36-46
references.pmid: 19960040
references.citation: J Biol Chem. 2008 Dec 12;283(50):34833-43
references.pmid: 18945671
references.citation: Front Biosci. 2008 Jan 01;13:453-61
references.pmid: 17981560
references.citation: J Lipid Res. 2009 Apr;50 Suppl:S382-7
references.pmid: 18953058
references.citation: Front Immunol. 2011 Nov 08;2:57
references.pmid: 22566847
references.citation: J Mol Neurosci. 2010 Jan;40(1-2):87-90
references.pmid: 19705088
references.citation: Brain Res. 2009 Feb 23;1256:1-7
references.pmid: 19063868
references.citation: J Cell Biochem. 2011 Aug;112(8):1978-84
references.pmid: 21541985
references.citation: J Leukoc Biol. 2009 Jul;86(1):13-22
references.pmid: 19201987
references.citation: Arterioscler Thromb Vasc Biol. 2011 Jul;31(7):1506-16
references.pmid: 21677293
references.citation: Mol Pharmacol. 2003 Feb;63(2):311-24
references.pmid: 12527802
references.citation: Cancer Res. 2012 Sep 1;72(17):4440-8
references.pmid: 22728650
references.citation: Nat Immunol. 2005 Aug;6(8):844-51
references.pmid: 16025117
references.citation: Physiol Rev. 2009 Jan;89(1):73-120
references.pmid: 19126755
references.citation: Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2792-7
references.pmid: 22096099
references.citation: Antioxid Redox Signal. 2009 Sep;11(9):2333-9
references.pmid: 19243235
references.citation: J Med Chem. 2005 Feb 24;48(4):905-8
references.pmid: 15715459
references.citation: Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1419-23
references.pmid: 19696407
references.citation: Am J Clin Pathol. 2013 Mar;139(3):317-22
references.pmid: 23429367
references.citation: Biochem Biophys Res Commun. 2011 Jul 8;410(3):643-7
references.pmid: 21684255
references.citation: Pharm Res. 2011 Feb;28(2):413-6
references.pmid: 20859658
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D1144-9
references.pmid: 22086960
references.citation: J Leukoc Biol. 2009 Jul;86(1):1-3
references.pmid: 19567410
references.citation: Biochem Biophys Res Commun. 2011 Apr 8;407(2):432-7
references.pmid: 21414290
references.citation: Blood. 2003 Jul 1;102(1):344-52
references.pmid: 12637318
references.citation: Biochem Biophys Res Commun. 2012 Oct 12;427(1):178-84
references.pmid: 22989752
references.citation: Biochem Biophys Res Commun. 2009 Dec 4;390(1):148-54
references.pmid: 19785985
references.citation: PLoS One. 2010 Jan 25;5(1):e8852
references.pmid: 20111605
references.citation: Cell Death Differ. 2004 Apr;11(4):381-9
references.pmid: 14685163
references.citation: Nature. 2003 Jan 23;421(6921):384-8
references.pmid: 12508119
references.citation: J Mol Neurosci. 2010 Jan;40(1-2):211-6
references.pmid: 19714494
references.citation: Brain Res. 2010 Apr 30;1328:1-11
references.pmid: 20211606
references.citation: Acta Pharmacol Sin. 2009 Jun;30(6):673-80
references.pmid: 19448647
references.citation: Arterioscler Thromb Vasc Biol. 2010 Oct;30(10):1925-32
references.pmid: 20651282
references.citation: Mol Hum Reprod. 2005 Dec;11(12):881-9
references.pmid: 16421212
references.citation: Cardiovasc Res. 2014 Jan 1;101(1):138-44
references.pmid: 24101197
references.citation: Nucleic Acids Res. 2010 Jan;38(Database issue):D792-9
references.pmid: 19906719
references.citation: Life Sci. 2007 May 30;80(24-25):2314-9
references.pmid: 17383684