title: Dietary apigenin reduces LPS-induced expression of miR-155 restoring immune balance during inflammation.
abstract: METHODS
  High incidence of inflammatory diseases afflicts the increasing aging-population infringing a great health burden. Dietary flavonoids, including the flavone apigenin, are emerging as important anti-inflammatory nutraceuticals due to their health benefits, lack of adverse effects and reduced costs. MicroRNAs (miRs) play a central role in inflammation by regulating gene expression, yet how dietary ingredients affect miRs is poorly understood. The aim of this study was to identify miRs involved in the anti-inflammatory activity of apigenin and apigenin-rich diets and determine their immune regulatory mechanisms in macrophages and in vivo.
  
  
  RESULTS
  A high-throughput quantitative reverse transcriptase PCR screen of 312 miRs in macrophages revealed that apigenin reduced LPS-induced miR-155 expression. Analyses of miR-155 precursor and primary transcript indicated that apigenin regulated miR-155 transcriptionally. Apigenin-reduced expression of miR-155 led to the increase of anti-inflammatory regulators forkhead box O3a and smooth-muscle-actin and MAD-related protein 2 in LPS-treated macrophages. In vivo, apigenin or a celery-based apigenin-rich diet reduced LPS-induced expression of miR-155 and decreased tumor necrosis factor α in lungs from LPS-treated mice.
  
  
  CONCLUSIONS
  These results demonstrate that apigenin and apigenin-rich diets exert effective anti-inflammatory activity in vivo by reducing LPS-induced expression of miR-155, thereby restoring immune balance.
authors: Department of Physiology and Cell Biology, The Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; Department of Molecular Genetics, The Ohio State University, Columbus, OH, USA; Molecular Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH, USA.
authors: Daniel
authors: D
authors: Arango
authors: Mayra
authors: M
authors: Diosa-Toro
authors: Laura S
authors: LS
authors: Rojas-Hernandez
authors: Jessica L
authors: JL
authors: Cooperstone
authors: Steven J
authors: SJ
authors: Schwartz
authors: Xiaokui
authors: X
authors: Mo
authors: Jinmai
authors: J
authors: Jiang
authors: Thomas D
authors: TD
authors: Schmittgen
authors: Andrea I
authors: AI
authors: Doseff
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D000077102:Apium / Q000737:chemistry; D045744:Cell Line, Tumor; D004032:Diet; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D014409:Tumor Necrosis Factor-alpha; D047310:Apigenin
keywords: Flavonoids; Macrophages; MicroRNAs; NF-κB; Sepsis
references: Am J Clin Nutr. 2004 May;79(5):727-47
references: 15113710
references: Int J Mol Med. 2010 Dec;26(6):935-40
references: 21042790
references: Phytother Res. 2006 Jul;20(7):519-30
references: 16628544
references: J Virol. 2014 May;88(9):4798-810
references: 24522920
references: J Photochem Photobiol B. 2009 Jan 9;94(1):1-7
references: 18922698
references: J Immunol. 2007 Oct 15;179(8):5082-9
references: 17911593
references: Free Radic Biol Med. 2013 Sep;64:40-51
references: 23751562
references: J Biomed Sci. 2012 Jul 31;19:69
references: 22849760
references: J Agric Food Chem. 2012 Jan 11;60(1):202-8
references: 22224550
references: Nucleic Acids Res. 2013 Jan 7;41(1):542-53
references: 23143100
references: Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17408-13
references: 21969554
references: Int Immunol. 2012 Apr;24(4):253-65
references: 22331441
references: Blood. 2010 Dec 23;116(26):5885-94
references: 20852130
references: J Biol Chem. 2010 Dec 31;285(53):41328-36
references: 21036908
references: Nat Immunol. 2005 Dec;6(12):1179-81
references: 16369556
references: J Nutr Biochem. 2011 Mar;22(3):293-9
references: 20579867
references: Int J Cancer. 2009 Apr 15;124(8):1918-25
references: 19117058
references: BMC Genomics. 2009 Aug 28;10:407
references: 19715577
references: Science. 2002 Nov 8;298(5596):1241-5
references: 12424381
references: Nutr Clin Pract. 2010 Dec;25(6):634-40
references: 21139128
references: Biochem Pharmacol. 2006 Sep 14;72(6):681-92
references: 16844095
references: Genome Biol. 2007;8(11):R248
references: 18034880
references: Nat Rev Genet. 2014 Sep;15(9):599-612
references: 25022902
references: Int J Mol Sci. 2013 Aug 28;14(9):17664-79
references: 23989609
references: Inflamm Bowel Dis. 2014 Apr;20(4):652-9
references: 24583476
references: Nat Rev Mol Cell Biol. 2005 May;6(5):376-85
references: 15852042
references: Immunity. 2004 Aug;21(2):203-13
references: 15308101
references: N Engl J Med. 2018 Jun 21;378(25):2441-2442
references: 29897867
references: J Pharm Pharm Sci. 2013;16(5):821-47
references: 24393558
references: FASEB J. 2009 Sep;23(9):2898-908
references: 19423639
references: Mol Nutr Food Res. 2013 Jan;57(1):58-70
references: 23165995
references: Nucleic Acids Res. 2014 Jan;42(2):882-92
references: 24165878
references: J Immunol. 2007 Nov 15;179(10):7121-7
references: 17982104
references: Nat Rev Immunol. 2008 Oct;8(10):776-87
references: 18802444
references: Methods. 2008 Jan;44(1):31-8
references: 18158130
references: J Mol Cell Cardiol. 1998 Apr;30(4):723-31
references: 9602421
references: Am J Nephrol. 2010;32(5):462-8
references: 20948191
references: Nat Rev Cardiol. 2009 Jun;6(6):399-409
references: 19399028
references: Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9619-24
references: 19487661
references: J Biol Chem. 2011 Jan 14;286(2):1436-44
references: 21062749
references: J Infect Dis. 2009 Sep 15;200(6):916-25
references: 19650740
references: Biochem Pharmacol. 2012 Dec 15;84(12):1571-80
references: 22985621
references: Neurochem Int. 2008 Mar-Apr;52(4-5):878-86
references: 18037535
references: Cell Death Dis. 2010 Aug 19;1:e64
references: 21364669
references: PLoS One. 2013 Nov 21;8(11):e79757
references: 24278171
references: Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):E2153-62
references: 23697369
references: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1604-9
references: 17242365
references: Mol Nutr Food Res. 2012 Apr;56(4):558-69
references: 22351119
references: Int J Mol Sci. 2013 Dec 09;14(12):23910-21
references: 24351865
references: Nat Immunol. 2008 Aug;9(8):839-45
references: 18645592
references: Sci Rep. 2013;3:2553
references: 23989853
references: Nat Rev Immunol. 2009 Nov;9(11):778-88
references: 19855404