title: Toll-like receptor 4, F4/80 and pro-inflammatory cytokines in intestinal and mesenteric fat tissue of Crohn's disease.
abstract: BACKGROUND
  Crohn's disease (CD) is a chronic intestinal ailment with a multifactorial etiology, whose incidence has increased during the last three decades. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected nearby the affected intestinal area; however, there are few studies on this aspect.
  
  
  OBJECTIVE
  To evaluate inflammatory activity in intestinal mucosa and mesenteric fat tissue of patients with CD and controls.
  
  
  METHODS
  Ten patients with ileocecal CD and 16 patients with non-inflammatory disease (control groups) were studied. The specimens were snap-frozen and the expression of TLR-4, F4/80, IL1-β and IL-6 were determined by immunoblot of protein extracts. TLR4 RNA level were measured using RT-PCR. The t Test was applied (p<0.05). The local ethical committee approved the study.
  
  
  RESULTS
  The intestinal mucosa of CD group had significantly higher protein levels of TLR-4, F4/80, IL-1β and IL-6 than the controls. The gene expression of TLR4 was lower in the intestinal mucosa of CD compared to the control group. Regard the mesenteric fat tissue, there was no statistical difference related to TLR-4, F4/80, IL-1β and IL-6 proteins expression.
  
  
  CONCLUSIONS
  These findings may result from an up-regulation of macrophage activation and intracellular pathways activated by bacterial antigens, which are more important in intestinal mucosa than fat tissue in CD patients. This may represent an anomalous regulation of innate immunity and could contribute to the production of proinflammatory mediators and disease development.
authors: Coloproctology Unit, Surgery Department, University of Campinas (UNICAMP), Medical School São Paulo, Brazil ; Laboratory of Cell Signaling, Internal Medicine Department University of Campinas (UNICAMP), Medical School São Paulo, Brazil.
authors: Raquel F
authors: RF
authors: Leal
authors: Marciane
authors: M
authors: Milanski
authors: Maria de Lourdes S
authors: Mde L
authors: Ayrizono
authors: Andressa
authors: A
authors: Coope
authors: Viviane S
authors: VS
authors: Rodrigues
authors: Mariana
authors: M
authors: Portovedo
authors: Luiza M F
authors: LM
authors: Oliveira
authors: João J
authors: JJ
authors: Fagundes
authors: Cláudio S R
authors: CS
authors: Coy
authors: Lício A
authors: LA
authors: Velloso
keywords: Crohn’s disease; cytokines; inflammatory bowel disease; innate immunity
references: Gastroenterology. 1976 Mar;70(3):439-44
references: 1248701
references: Inflamm Bowel Dis. 2011 Mar;17(3):747-57
references: 20684014
references: Immunity. 2009 Sep 18;31(3):513-25
references: 19733489
references: Clin Exp Immunol. 1993 Oct;94(1):174-81
references: 8403503
references: Annu Rev Immunol. 2002;20:197-216
references: 11861602
references: J Exp Med. 2009 Dec 21;206(13):3101-14
references: 20008524
references: Gut. 2012 Jan;61(1):86-94
references: 21930728
references: Gastroenterol Clin Biol. 2003 Nov;27(11):987-91
references: 14732844
references: Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12490-5
references: 8901609
references: Infect Immun. 2000 Dec;68(12):7010-7
references: 11083826
references: Gut. 2008 Feb;57(2):181-7
references: 17639086
references: Gut. 2002 Sep;51(3):379-85
references: 12171960
references: Int J Colorectal Dis. 2009 Jan;24(1):1-4
references: 18815796
references: Gut. 1998 Apr;42(4):477-84
references: 9616307
references: J Biol Chem. 2000 Aug 11;275(32):24255-63
references: 10823826
references: Gut. 2012 Jan;61(1):78-85
references: 21940721
references: Gastroenterology. 2011 May;140(6):1785-94
references: 21530745
references: J Immunol. 2010 Feb 15;184(4):2026-37
references: 20089703
references: J Gastroenterol Hepatol. 2006 Sep;21(9):1412-8
references: 16911685
references: Gut. 2005 Jun;54(6):789-96
references: 15888786
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: Br J Surg. 1992 Sep;79(9):955-8
references: 1422768
references: Eur J Immunol. 1996 May;26(5):1139-46
references: 8647179
references: Gut. 2007 Apr;56(4):577-83
references: 16956921
references: Immunology. 2008 Oct;125(2):145-53
references: 18798918
references: Inflamm Bowel Dis. 2006 Jun;12(6):471-7
references: 16775490
references: Gastroenterology. 1999 Jul;117(1):73-81
references: 10381912
references: Ann N Y Acad Sci. 2006 Aug;1072:407-9
references: 17057223
references: Clin Gastroenterol Hepatol. 2011 Aug;9(8):684-687.e1
references: 21642015
references: J Gastroenterol Hepatol. 2006 Sep;21(9):1419-23
references: 16911686