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.

DESIGN:

Interventional laboratory study.

SETTING:

Academic medical research center.

SUBJECTS:

Four-week-old C57BL/6 wild-type (n = 12) and C57BL/6 TLR2-deficient mice (TLR2-/-) (n = 12).

INTERVENTIONS:

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.

MEASUREMENTS AND MAIN 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: Charles J Aprahamian, Robin G Lorenz, Carroll M Harmon, Reed A Dimmit
• Journal: Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies (Pediatr Crit Care Med) Vol. 9 Issue 1 Pg. 105-9 (Jan 2008) ISSN: 1529-7535 [Print] United States
• PMID: 17906593 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Toll-Like Receptor 2

Topics

• Academic Medical Centers
• Animals
• Immunity, Mucosal
• Intestine, Small (injuries)
• Laparotomy
• Mesenteric Vascular Occlusion
• Mice
• Mice, Knockout
• Models, Animal
• Mucous Membrane (injuries)
• Reperfusion Injury (immunology)
• Toll-Like Receptor 2 (immunology, metabolism)