title: Toll-like receptor 2 is protective of ischemia-reperfusion-mediated small-bowel injury in a murine model.
abstract: OBJECTIVE
  In a murine model of intestinal injury, we hypothesized that Toll-like receptor 2 (TLR2), a recognition molecule for commensal bacteria, plays an important role in the development of mucosal immunity and is protective against ischemia/reperfusion injury via the modulation of both innate and acquired immunity.
  
  
  METHODS
  Interventional laboratory study.
  
  
  METHODS
  Academic medical research center.
  
  
  METHODS
  Four-week-old C57BL/6 wild-type (n = 12) and C57BL/6 TLR2-deficient mice (TLR2-/-) (n = 12).
  
  
  METHODS
  Twenty-four mice underwent laparotomy only or laparotomy plus superior mesenteric artery occlusion (n = 6/group) for 60 mins, followed by 90 mins of recovery.
  
  
  RESULTS
  Mid-jejunal sections were taken for histopathology and messenger RNA expression (reverse transcriptase-polymerase chain reaction, normalized to 18s and laparotomy-only controls). Intestinal injury was scored from 0 (no injury) to 4 (transmural necrosis). Statistical analyses were performed using Mann-Whitney U test and Student's t-test (p < .05 significant). TLR2-/- mice had elevated intestinal injury scores (mean +/- SEM) after ischemia/reperfusion vs. wild-type (2.17 +/- 0.40 vs. 0.67 +/- 0.33, p < .05). Intestinal cytokine messenger RNA (mean fold change +/- SEM) of interferon-gamma (0.29 +/- 0.12 vs. 3313 +/- 1710), interleukin-4 (0.25 +/- 0.13 vs. 2.70 +/- 1.08), and interleukin-6 (250.63 +/- 69.60 vs. 320,300 +/- 215,964) in TLR2-/- was significantly decreased (p < .05) after ischemia/reperfusion vs. wild-type. Tumor necrosis factor-alpha messenger RNA levels were unchanged.
  
  
  CONCLUSIONS
  TLR2-/- mice have a dysregulated mucosal innate immune response and fail to mount a protective response after ischemia-reperfusion compared with wild-type mice. This murine model of intestinal injury may correlate with the early postnatal course of premature infants who may have decreased TLR2 expression and/or decreased luminal commensal bacteria secondary to antibiotic therapy, thus decreasing TLR2-mediated signaling.
authors: Department of Surgery, University of Alabama at Birmingham, USA. Charles.Aprahamian@ccc.uab.edu
authors: Charles J
authors: CJ
authors: Aprahamian
authors: Robin G
authors: RG
authors: Lorenz
authors: Carroll M
authors: CM
authors: Harmon
authors: Reed A
authors: RA
authors: Dimmit
mesh_terms: D000046:Academic Medical Centers; D000818:Animals; D018928:Immunity, Mucosal; D007421:Intestine, Small / Q000293:injuries*; D007813:Laparotomy; D008641:Mesenteric Vascular Occlusion; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009092:Mucous Membrane / Q000293:injuries; D015427:Reperfusion Injury / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism
chemical_list: D051195:Toll-Like Receptor 2