title: The Myc 3' Wnt responsive element regulates neutrophil recruitment after acute colonic injury in mice.
abstract: BACKGROUND
  The Wnt/β-catenin pathway regulates intestinal development, homeostasis, and regeneration after injury. Wnt/β-catenin signaling drives intestinal proliferation by activating expression of the c-Myc proto-oncogene (Myc) through the Myc 3' Wnt responsive DNA element (Myc 3' WRE). In a previous study, we found that deletion of the Myc 3' WRE in mice caused increased MYC expression and increased cellular proliferation in the colon. When damaged by dextran sodium sulfate (DSS), the increased proliferative capacity of Myc 3' WRE(-/-) colonocytes resulted in a more rapid recovery compared with wild-type (WT) mice. In that study, we did not examine involvement of the immune system in colonic regeneration.
  
  
  OBJECTIVE
  To characterize the innate immune response in Myc 3' WRE(-/-) and WT mice during and after DSS-induced colonic injury.
  
  
  METHODS
  Mice were fed 2.5 % DSS in their drinking water for five days to induce colonic damage and were then returned to normal water for two or four days to recover. Colonic sections were prepared and neutrophils and macrophages were analyzed by immunohistochemistry. Cytokine and chemokine levels were analyzed by probing a cytokine array with colonic lysates.
  
  
  RESULTS
  In comparison with WT mice, there was enhanced leukocyte infiltration into the colonic mucosal and submucosal layers of Myc 3' WRE(-/-) mice after DSS damage. Levels of activated neutrophils were substantially increased in damaged Myc 3' WRE(-/-) colons as were levels of the neutrophil chemoattractants C5/C5a, CXCL1, and CXCL2.
  
  
  CONCLUSIONS
  The Myc 3' WRE regulates neutrophil infiltration into DSS-damaged colons.
authors: The Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Dr. H171, Hershey, PA 17033, USA.
authors: Wesley M
authors: WM
authors: Konsavage
authors: The Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Dr. H171, Hershey, PA 17033, USA.
authors: Jennifer N
authors: JN
authors: Roper
authors: The Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Dr. H171, Hershey, PA 17033, USA.
authors: Faoud T
authors: FT
authors: Ishmael
authors: The Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Dr. H171, Hershey, PA 17033, USA.
authors: Gregory S
authors: GS
authors: Yochum
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000503:physiopathology; D003108:Colonic Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D012038:Regeneration / Q000235:genetics / Q000502:physiology; D020218:Response Elements / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D018925:Chemokines; D016207:Cytokines; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D051153:Wnt Proteins; D016264:Dextran Sulfate
references: Nat Rev Mol Cell Biol. 2009 Apr;10(4):276-86
references: 19305417
references: J Pharmacol Exp Ther. 2009 Apr;329(1):123-9
references: 19131582
references: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3324-9
references: 17360646
references: J Intern Med. 2012 May;271(5):421-8
references: 22324936
references: J Immunol. 2009 Dec 1;183(11):7514-22
references: 19917676
references: Inflamm Bowel Dis. 2008 Sep;14(9):1229-35
references: 18398894
references: Inflamm Bowel Dis. 2011 Aug;17(8):1651-64
references: 21744421
references: J Immunol. 2008 Mar 15;180(6):4308-15
references: 18322244
references: J Leukoc Biol. 2000 Mar;67(3):267-78
references: 10733087
references: J Leukoc Biol. 2001 Jun;69(6):899-906
references: 11404374
references: Dig Dis Sci. 2006 Jul;51(7):1260-8
references: 16944023
references: Mol Cancer Ther. 2007 Sep;6(9):2399-408
references: 17876039
references: Adv Drug Deliv Rev. 2007 Sep 30;59(11):1073-83
references: 17825455
references: Eur J Immunol. 2012 Dec;42(12):3358-68
references: 23027555
references: J Leukoc Biol. 2000 Jun;67(6):757-66
references: 10857846
references: J Invest Dermatol. 1982 Mar;78(3):206-9
references: 6276474
references: Mol Cell Biol. 2008 Dec;28(24):7368-79
references: 18852287
references: Cell. 2011 Sep 16;146(6):904-17
references: 21889194
references: Cell. 2010 Apr 30;141(3):432-45
references: 20434984
references: Crit Care. 2004 Dec;8(6):453-61
references: 15566616
references: Dev Cell. 2009 Jul;17(1):9-26
references: 19619488
references: J Am Chem Soc. 2009 Jun 3;131(21):7390-401
references: 19432426
references: Innate Immun. 2008 Apr;14(2):117-24
references: 18713728
references: Can J Gastroenterol. 2002 Apr;16(4):241-6
references: 11981577
references: Mucosal Immunol. 2012 Mar;5(2):194-206
references: 22258450
references: Dev Cell. 2010 Aug 17;19(2):259-69
references: 20708588
references: Genes Dev. 2008 Oct 15;22(20):2755-66
references: 18923074
references: Nat Protoc. 2007;2(3):541-6
references: 17406617
references: Exp Cell Res. 2011 Nov 15;317(19):2719-24
references: 21787769
references: Crit Rev Immunol. 2008;28(6):467-83
references: 19265505
references: Mol Cell Biol. 2012 Oct;32(19):3891-902
references: 22826434
references: Genes Dev. 2003 Jul 15;17(14):1709-13
references: 12865297
references: J Pharmacol Toxicol Methods. 1998 Apr;39(3):169-78
references: 9741392
references: Cell. 2012 Jun 8;149(6):1192-205
references: 22682243
references: Nat Rev Immunol. 2011 Jan;11(1):9-20
references: 21151034
references: World J Gastroenterol. 2012 Apr 21;18(15):1708-22
references: 22553395
references: Semin Cancer Biol. 2006 Aug;16(4):253-64
references: 16904903
references: J Interferon Cytokine Res. 2009 Jun;29(6):313-26
references: 19441883
references: J Leukoc Biol. 2007 Nov;82(5):1239-46
references: 17656654
references: Gut. 2005 Mar;54(3):364-8
references: 15710984
references: Nat Med. 2012 Mar 11;18(4):618-23
references: 22406745
references: Biochim Biophys Acta. 2012 Oct;1822(10):1600-7
references: 22750333
references: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):145-50
references: 19966299
references: Gastroenterology. 2011 Jul;141(1):259-68, 268.e1-8
references: 21440550
references: Science. 1998 Sep 4;281(5382):1509-12
references: 9727977
references: Clin Vaccine Immunol. 2010 Nov;17(11):1797-809
references: 20826612
references: Genes Dev. 2003 May 1;17(9):1115-29
references: 12695333
references: Annu Rev Cell Dev Biol. 2004;20:695-723
references: 15473857
references: Dig Dis Sci. 2011 Jan;56(1):79-89
references: 20467900