title: Complement protein C1q promotes macrophage anti-inflammatory M2-like polarization during the clearance of atherogenic lipoproteins.
abstract: OBJECTIVE
  Innate immune protein C1q plays a dual role in the chronic inflammatory disease of atherosclerosis. Complement activation via C1q exacerbates pathology in the atherosclerotic lesion in later stages of the disease. However, in early stages of disease C1q is protective. We hypothesize that complement-independent activities of C1q are involved in reprogramming macrophage inflammatory polarization.
  
  
  METHODS
  The influence of C1q on macrophage inflammatory responses during clearance of oxLDL was examined. Changes in cytokines at the gene and protein level were measured by quantitative PCR and ELISA assay.
  
  
  RESULTS
  C1q modulated cytokine expression in Raw264.7 macrophages during ingestion of oxLDL. Levels of pro-inflammatory cytokines IL-1β and IL-6 were downregulated by C1q, whereas levels of the anti-inflammatory cytokine IL-10 were increased. In addition, data from an NFκB-luciferase gene reporter assay suggest that C1q suppresses activation of NFκB during lipoprotein clearance in macrophages, providing one mechanism by which C1q downregulates pro-inflammatory cytokine production.
  
  
  CONCLUSIONS
  C1q-polarization of macrophages toward an anti-inflammatory (M2-like) phenotype may be important in dampening inflammation in the early atherosclerotic lesion. Further investigation of molecular pathways targeted by C1q may provide novel therapeutic targets for this disease.
authors.affiliation: Department of Biological Sciences, California State University Long Beach, 1250 Bellflower Blvd, Long Beach, CA, 90840, USA.
authors.forename: Weston
authors.initials: W
authors.lastname: Spivia
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Magno
authors.forename: Patrick
authors.initials: P
authors.lastname: Le
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Fraser
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D015922:Complement C1q / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics
chemical_list: D016207:Cytokines; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D015922:Complement C1q
references.citation: J Immunol. 2012 Apr 15;188(8):3716-23
references.pmid: 22422887
references.citation: J Neurochem. 2010 Feb;112(3):733-43
references.pmid: 19919576
references.citation: Curr Opin Lipidol. 2011 Oct;22(5):335-42
references.pmid: 21841486
references.citation: Curr Drug Targets. 2008 Feb;9(2):113-22
references.pmid: 18288962
references.citation: Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1419-23
references.pmid: 19696407
references.citation: Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7166-71
references.pmid: 21482781
references.citation: Curr Opin Lipidol. 2012 Oct;23(5):429-38
references.pmid: 22964992
references.citation: Arterioscler Thromb Vasc Biol. 2005 May;25(5):904-14
references.pmid: 15731497
references.citation: NCHS Data Brief. 2011 Jul;(64):1-8
references.pmid: 22142873
references.citation: J Biol Chem. 2007 Mar 9;282(10):7360-7
references.pmid: 17209050
references.citation: FASEB J. 2010 Aug;24(8):2869-80
references.pmid: 20354139
references.citation: Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a001651
references.pmid: 20457564
references.citation: Curr Opin Lipidol. 2008 Oct;19(5):478-82
references.pmid: 18769228
references.citation: Arterioscler Thromb Vasc Biol. 1998 Nov;18(11):1790-5
references.pmid: 9812919
references.citation: J Leukoc Biol. 2012 Sep;92(3):489-97
references.pmid: 22715140
references.citation: Immunobiology. 2011 Nov;216(11):1172-6
references.pmid: 21802768
references.citation: J Atheroscler Thromb. 2010 Feb;17(1):97-105
references.pmid: 20093780
references.citation: Arterioscler Thromb Vasc Biol. 2003 Apr 1;23(4):656-60
references.pmid: 12615675
references.citation: Immunobiology. 1998 Aug;199(2):265-85
references.pmid: 9777411
references.citation: J Immunol. 2001 Oct 1;167(7):4033-7
references.pmid: 11564823
references.citation: Nat Genet. 1998 May;19(1):56-9
references.pmid: 9590289
references.citation: Cardiol Rev. 2014 May-Jun;22(3):147-51
references.pmid: 24618929
references.citation: Cardiovasc Res. 2004 Mar 1;61(4):671-82
references.pmid: 14985064
references.citation: J Immunol. 2012 Jun 1;188(11):5682-93
references.pmid: 22523386
references.citation: Biochim Biophys Acta. 2000 Dec 15;1529(1-3):164-74
references.pmid: 11111086
references.citation: Cell Metab. 2011 May 4;13(5):540-9
references.pmid: 21531336
references.citation: J Biol Chem. 2012 Jul 6;287(28):23479-88
references.pmid: 22613713
references.citation: Eur J Immunol. 2003 Oct;33(10):2853-63
references.pmid: 14515269
references.citation: Nature. 2010 Apr 29;464(7293):1357-61
references.pmid: 20428172
references.citation: Inflamm Res. 2009 Dec;58(12):909-19
references.pmid: 19603257
references.citation: Dev Immunol. 2002 Sep;9(3):151-9
references.pmid: 12892049
references.citation: Atherosclerosis. 2012 Dec;225(2):461-8
references.pmid: 23078881
references.citation: Circulation. 2002 Jun 25;105(25):3025-31
references.pmid: 12081998
references.citation: J Biol Chem. 2000 Apr 28;275(17):12633-8
references.pmid: 10777555
references.citation: J Immunol. 1997 May 15;158(10):4525-8
references.pmid: 9144462
references.citation: Annu Rev Pathol. 2006;1:297-329
references.pmid: 18039117
references.citation: J Immunol. 2010 Oct 1;185(7):3932-9
references.pmid: 20833838
references.citation: Am J Pathol. 2007 Jan;170(1):416-26
references.pmid: 17200212
references.citation: Cell Signal. 2012 Jun;24(6):1215-21
references.pmid: 22349240
references.citation: J Immunol. 2004 Sep 1;173(5):3044-50
references.pmid: 15322164
references.citation: Oncoimmunology. 2012 Nov 1;1(8):1227-1238
references.pmid: 23243586
references.citation: Mol Immunol. 2007 Jan;44(1-3):33-43
references.pmid: 16908067
references.citation: Circ Res. 2011 Jan 21;108(2):235-48
references.pmid: 21252151
references.citation: J Immunol. 2009 Nov 15;183(10):6175-85
references.pmid: 19864605
references.citation: Arterioscler Thromb Vasc Biol. 2001 Jul;21(7):1214-9
references.pmid: 11451754
references.citation: Biochem Biophys Res Commun. 2012 Aug 24;425(2):121-6
references.pmid: 22796220