title: Mitochondrial G protein coupled receptor kinase 2 regulates proinflammatory responses in macrophages.
abstract: G-protein-coupled receptor kinase 2 (GRK2) levels are elevated in inflammation but its role is not clear yet. Here we show that GRK2 expression is dependent on NFκB transcriptional activity. In macrophages, LPS induces GRK2 accumulation in mitochondria increasing biogenesis. The overexpression of the carboxy-terminal domain of GRK2 (βARK-ct), known to displace GRK2 from plasma membranes, induces earlier localization of GRK2 to mitochondria in response to LPS leading to increased mt-DNA transcription and reduced ROS production and cytokine expression. Our study shows the relevance of GRK2 subcellular localization in macrophage biology and its potential therapeutic properties in inflammation.
authors.affiliation: Dipartimento di Scienze Biomediche Avanzate, Università Federico II, Napoli, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Sorriento
authors.forename: A
authors.initials: A
authors.lastname: Fusco
authors.forename: M
authors.initials: M
authors.lastname: Ciccarelli
authors.forename: A
authors.initials: A
authors.lastname: Rungi
authors.forename: A
authors.initials: A
authors.lastname: Anastasio
authors.forename: A
authors.initials: A
authors.lastname: Carillo
authors.forename: G W
authors.initials: GW
authors.lastname: Dorn
authors.forename: B
authors.initials: B
authors.lastname: Trimarco
authors.forename: G
authors.initials: G
authors.lastname: Iaccarino
mesh_terms: D000818:Animals; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D054769:G-Protein-Coupled Receptor Kinase 2
keywords: G protein coupled receptor kinase 2; GRK2; Inflammation; LPS; Mitochondria; NFκB; ROS; Subcellular localization; lypolysaccharide; nuclear factor kappa B; reactive oxygen species; βARK-ct
references.citation: Crit Care Med. 2007 Sep;35(9 Suppl):S441-8
references.pmid: 17713391
references.citation: J Thromb Haemost. 2009 Nov;7(11):1920-8
references.pmid: 19740101
references.citation: J Leukoc Biol. 2006 Dec;80(6):1214-21
references.pmid: 16943386
references.citation: Am J Cardiovasc Dis. 2011;1(2):126-37
references.pmid: 22254193
references.citation: Pharmacol Ther. 2012 Jan;133(1):40-69
references.pmid: 21903131
references.citation: Biochim Biophys Acta. 2012 Apr;1820(4):532-41
references.pmid: 22265687
references.citation: J Neuroimmunol. 2004 Oct;155(1-2):143-9
references.pmid: 15342205
references.citation: Mol Cancer Res. 2007 Jun;5(6):627-39
references.pmid: 17579121
references.citation: Circ Res. 2005 Nov 25;97(11):1182-9
references.pmid: 16239589
references.citation: J Cell Physiol. 2011 Mar;226(3):627-37
references.pmid: 20717897
references.citation: Curr Biol. 2006 Oct 24;16(20):2042-7
references.pmid: 17055984
references.citation: Circulation. 2011 May 10;123(18):1953-62
references.pmid: 21518983
references.citation: Trends Pharmacol Sci. 2007 Apr;28(4):173-9
references.pmid: 17350109
references.citation: J Immunol. 2001 Feb 1;166(3):1635-40
references.pmid: 11160205
references.citation: Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2180-5
references.pmid: 9122168
references.citation: Nat Rev Mol Cell Biol. 2002 Sep;3(9):639-50
references.pmid: 12209124
references.citation: J Biol Chem. 2012 Apr 13;287(16):12771-8
references.pmid: 22389501
references.citation: J Immunol. 2005 Apr 1;174(7):4400-6
references.pmid: 15778405
references.citation: Br J Pharmacol. 2011 Feb;162(3):712-21
references.pmid: 20958287
references.citation: Cardiovasc Res. 2009 Dec 1;84(3):407-15
references.pmid: 19620130
references.citation: Biochem J. 2009 Dec 14;425(1):169-78
references.pmid: 19796012
references.citation: Eur Heart J. 2013 May;34(19):1437-47
references.pmid: 22261894
references.citation: Mol Cancer. 2009 Nov 09;8:97
references.pmid: 19900276
references.citation: J Neuroimmunol. 2003 Apr;137(1-2):79-86
references.pmid: 12667650
references.citation: Br J Pharmacol. 2010 Jun;160(4):821-32
references.pmid: 20590581
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17818-23
references.pmid: 19008357
references.citation: Annu Rev Pharmacol Toxicol. 1998;38:289-319
references.pmid: 9597157
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12457-62
references.pmid: 18711143
references.citation: J Cell Physiol. 2011 May;226(5):1323-33
references.pmid: 20945396
references.citation: FASEB J. 1999 Apr;13(6):715-25
references.pmid: 10094932
references.citation: Circ Res. 2013 Apr 12;112(8):1121-34
references.pmid: 23467820
references.citation: Am J Respir Crit Care Med. 2007 Oct 15;176(8):768-77
references.pmid: 17600279
references.citation: Nat Immunol. 2002 Mar;3(3):221-7
references.pmid: 11875461
references.citation: Annu Rev Physiol. 2007;69:561-77
references.pmid: 17002595
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1442-7
references.pmid: 15671181
references.citation: Mol Pharmacol. 2000 Apr;57(4):826-31
references.pmid: 10727532
references.citation: Biochim Biophys Acta. 2007 Apr;1768(4):913-22
references.pmid: 17084806
references.citation: Cell Signal. 2003 Nov;15(11):973-81
references.pmid: 14499340
references.citation: Cell Adh Migr. 2009 Jan-Mar;3(1):19-23
references.pmid: 19372742
references.citation: Annu Rev Physiol. 2007;69:511-34
references.pmid: 17305472
references.citation: Blood. 2006 Nov 1;108(9):2906-13
references.pmid: 16849637
references.citation: Cardiovasc Res. 2006 Jan;69(1):46-56
references.pmid: 16288730
references.citation: Cell Signal. 2012 Feb;24(2):468-475
references.pmid: 21983013
references.citation: Clin Pharmacol Ther. 2006 Dec;80(6):633-45
references.pmid: 17178264
references.citation: Circulation. 2004 Jun 1;109(21):2587-93
references.pmid: 15136501
references.citation: Curr Pharm Des. 2012;18(2):121-7
references.pmid: 22229580