title: Requirement of epithelial integrin-linked kinase for facilitation of Citrobacter rodentium-induced colitis.
abstract: BACKGROUND
  Integrin-linked kinase (ILK) is a serine-threonine kinase that transduces extracellular matrix-related cues into intracellular signals, with fundamental roles in cell motility, development and cancer. Recently ILK been shown to have an important role in bacterial epithelial cell attachment, through ILK-bacterial OspE binding. Here we report on the role of epithelial derived ILK in response to Citrobacter rodentium infection.
  
  
  METHODS
  C. rodentium was administered to both control and intestinal epithelial cell ILK knockout mice. Histological inflammatory scores were assessed, and cytokines measured by ELISA as well as RT-PCR, in mouse colons. Bacterial colonization was determined by plating homogenates onto MacConkey agar, and immunofluorescence microscopy performed using anti-LPS and anti-Tir antibodies.
  
  
  RESULTS
  ILK-ko mice exhibited reduced weight loss at 15 days post-infection (p < 0.01) and demonstrated reduced histological inflammatory scores (p < 0.01), reduced CCL2 and pro-inflammatory cytokines. This was not due to reduced colonization, but was associated with an altered pattern of C. rodentium bacterial migration. Attenuated fibronectin expression was found in the ILK-ko mice. C. rodentium exposure was shown to increase ILK expression in cell lines, and in murine epithelium in vivo. In ILK-ko mice reduced activation of ser473Akt and reduced crypt proliferation, together with reduced cyclin D1 expression were observed.
  
  
  CONCLUSIONS
  ILK influences the host response to C. rodentium -induced infection, independently of reduced colonization in the ILK knockout mice. The reduced inflammation and dramatically attenuated hyperplastic cryptal response to infection in this group, are at least in part the result of, the reduction in CCL2 and cyclin D1 expression respectively.
authors.affiliation: Division of Gastroenterology, Department of Medicine, The University of British Columbia, 5th Floor, 2775 Laurel Street, V5Z 1M9 Vancouver, BC, Canada. bill.salh@ubc.ca.
authors.forename: Kiran
authors.initials: K
authors.lastname: Assi
authors.forename: Kirk
authors.initials: K
authors.lastname: Bergstrom
authors.forename: Bruce
authors.initials: B
authors.lastname: Vallance
authors.forename: David
authors.initials: D
authors.lastname: Owen
authors.forename: Baljinder
authors.initials: B
authors.lastname: Salh
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology; D044082:Citrobacter rodentium; D003092:Colitis / Q000209:etiology / Q000276:immunology*; D019938:Cyclin D1 / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000150:complications / Q000276:immunology*; D005353:Fibronectins / Q000276:immunology; D045325:HCT116 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D000099200:Scaffold Protein ILK
chemical_list: D018932:Chemokine CCL2; D019938:Cyclin D1; D016207:Cytokines; D005353:Fibronectins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000099200:Scaffold Protein ILK; C491768:Ccl2 protein, mouse; C530105:Ccnd1 protein, mouse
references.citation: PLoS Pathog. 2010 May 13;6(5):e1000902
references.pmid: 20485566
references.citation: BMC Immunol. 2011 Aug 01;12:42
references.pmid: 21806815
references.citation: Cell Microbiol. 2006 Feb;8(2):257-66
references.pmid: 16441436
references.citation: J Cell Biol. 2011 Dec 26;195(7):1083-92
references.pmid: 22123833
references.citation: J Cell Sci. 2008 Oct 1;121(Pt 19):3121-32
references.pmid: 18799788
references.citation: Cancer Res. 2001 Apr 1;61(7):2899-906
references.pmid: 11306465
references.citation: Microbes Infect. 2001 Apr;3(4):333-40
references.pmid: 11334751
references.citation: Br J Cancer. 2003 Jun 2;88(11):1755-62
references.pmid: 12771992
references.citation: Infect Immun. 2002 Apr;70(4):2070-81
references.pmid: 11895973
references.citation: Am J Pathol. 2010 Sep;177(3):1320-32
references.pmid: 20651246
references.citation: Virchows Arch. 2010 Mar;456(3):261-8
references.pmid: 20091050
references.citation: Infect Immun. 2011 May;79(5):1863-72
references.pmid: 21343355
references.citation: Br J Pharmacol. 2006 Jul;148(6):814-24
references.pmid: 16751795
references.citation: Oncogene. 2001 Jan 4;20(1):133-40
references.pmid: 11244511
references.citation: Emerg Med Clin North Am. 2011 May;29(2):211-37, vii-viii
references.pmid: 21515177
references.citation: Int J Med Microbiol. 2003 Apr;293(1):87-93
references.pmid: 12755369
references.citation: Nature. 2009 May 28;459(7246):578-82
references.pmid: 19489119
references.citation: Expert Opin Pharmacother. 2012 Jan;13(1):17-26
references.pmid: 22106840
references.citation: Infect Immun. 2007 Jul;75(7):3271-81
references.pmid: 17470543
references.citation: Immunology. 2006 May;118(1):112-21
references.pmid: 16630028
references.citation: J Biol Chem. 2010 Oct 22;285(43):33485-33498
references.pmid: 20710027
references.citation: J Cell Physiol. 2010 Feb;222(2):387-400
references.pmid: 19885839
references.citation: Nat Rev Immunol. 2004 Dec;4(12):953-64
references.pmid: 15573130
references.citation: Exp Cell Res. 2009 Jan 1;315(1):97-109
references.pmid: 18996369
references.citation: Antioxid Redox Signal. 2011 Sep 1;15(5):1255-70
references.pmid: 21294654
references.citation: EMBO J. 2010 Jan 20;29(2):281-91
references.pmid: 20033063
references.citation: Nat Rev Cancer. 2005 Jan;5(1):51-63
references.pmid: 15630415
references.citation: J Biol Chem. 2000 Oct 20;275(42):32649-57
references.pmid: 10915780
references.citation: Eur J Cell Biol. 2011 Nov;90(11):891-6
references.pmid: 21561684
references.citation: Gut. 2008 Jul;57(7):931-40
references.pmid: 18326560
references.citation: Cell. 2009 Nov 25;139(5):871-90
references.pmid: 19945376
references.citation: Matrix Biol. 1999 Jun;18(3):211-23
references.pmid: 10429941