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Toll-like receptor 2 mediates ischemia-reperfusion injury of the small intestine in adult mice.

Watanabe T, Tanigawa T, Kobata A, Takeda S, Nadatani Y, Otani K, Yamagami H, Shiba M, Tominaga K, Fujiwara Y, Arakawa T - PLoS ONE (2014)

Bottom Line: Toll-like receptor 2 (TLR2) recognizes conserved molecular patterns associated with both gram-negative and gram-positive bacteria, and detects some endogenous ligands.TLR2 deficiency significantly inhibited the I/R-induced increase in MPO activity and the expression of mRNAs for TNF-α and ICAM-1, but did not affect the expression of COX-2 mRNA.TLR2 proteins were found to be expressed in the epithelial cells, inflammatory cells, and endothelial cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

ABSTRACT
Toll-like receptor 2 (TLR2) recognizes conserved molecular patterns associated with both gram-negative and gram-positive bacteria, and detects some endogenous ligands. Previous studies demonstrated that in ischemia-reperfusion (I/R) injury of the small intestine, the TLR2-dependent signaling exerted preventive effects on the damage in young mice, but did not have a significant effect in neonatal mice. We investigated the role of TLR2 in adult ischemia-reperfusion injury in the small intestine. Wild-type and TLR2 knockout mice at 16 weeks of age were subjected to intestinal I/R injury. Some wild-type mice received anti-Ly-6G antibodies to deplete circulating neutrophils. In wild-type mice, I/R induced severe small intestinal injury characterized by infiltration by inflammatory cells, disruption of the mucosal epithelium, and mucosal bleeding. Compared to wild-type mice, TLR2 knockout mice exhibited less severe mucosal injury induced by I/R, with a 35%, 33%, and 43% reduction in histological grading score and luminal concentration of hemoglobin, and the numbers of apoptotic epithelial cells, respectively. The I/R increased the activity of myeloperoxidase (MPO), a marker of neutrophil infiltration, and the levels of mRNA expression of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and cyclooxygenase-2 (COX-2) in the small intestine of the wild-type mice by 3.3-, 3.2-, and 13.0-fold, respectively. TLR2 deficiency significantly inhibited the I/R-induced increase in MPO activity and the expression of mRNAs for TNF-α and ICAM-1, but did not affect the expression of COX-2 mRNA. I/R also enhanced TLR2 mRNA expression by 2.9-fold. TLR2 proteins were found to be expressed in the epithelial cells, inflammatory cells, and endothelial cells. Neutrophil depletion prevented intestinal I/R injury in wild-type mice. These findings suggest that TLR2 may mediate I/R injury of the small intestine in adult mice via induction of inflammatory mediators such as TNF-α and ICAM-1.

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Effect of TLR2 deficiency on the expression of inflammatory mediators, neutrophil infiltration, and prostaglandin E2 synthesis after the ischemia-reperfusion injury of the small intestine.Wild-type (WT) mice and TLR2 knockout mice were subjected to 45 min of ischemia, followed by 60 min of reperfusion. After removing the small intestine, the mRNA expression levels for the tumor necrosis factor (TNF)-α (A), the intercellular adhesion molecule (ICAM)-1 (B), and cyclooxygenase (COX)-2 (C) were determined. Assays were also performed to estimate the myeloperoxidase (MPO) activity (a marker of neutrophil infiltration, D), and the prostaglandin E2 concentrations (E). Each column represents the mean ± SD. N = 6. *P<0.01 vs WT mice with sham operation, #P<0.01 vs WT mice subjected to the ischemia-reperfusion injury. I/R; ischemia/reperfusion
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pone-0110441-g002: Effect of TLR2 deficiency on the expression of inflammatory mediators, neutrophil infiltration, and prostaglandin E2 synthesis after the ischemia-reperfusion injury of the small intestine.Wild-type (WT) mice and TLR2 knockout mice were subjected to 45 min of ischemia, followed by 60 min of reperfusion. After removing the small intestine, the mRNA expression levels for the tumor necrosis factor (TNF)-α (A), the intercellular adhesion molecule (ICAM)-1 (B), and cyclooxygenase (COX)-2 (C) were determined. Assays were also performed to estimate the myeloperoxidase (MPO) activity (a marker of neutrophil infiltration, D), and the prostaglandin E2 concentrations (E). Each column represents the mean ± SD. N = 6. *P<0.01 vs WT mice with sham operation, #P<0.01 vs WT mice subjected to the ischemia-reperfusion injury. I/R; ischemia/reperfusion

Mentions: The intestinal I/R treatment increased expression levels of mRNAs for TNF-α, ICAM-1, and COX-2 in the small intestine of wild-type mice by 3.3-, 3.2-, and 13.0-fold, respectively (Figures 2A-2C). TLR2 deficiency prevented the I/R-induced increase in mRNAs for TNF-α and ICAM-1, but did not affect that in COX-2 mRNA. The I/R treatment also increased MPO activities in wild-type mice by 4.1-fold, but this effect was markedly inhibited in TLR2 KO mice (Figure 2D).


Toll-like receptor 2 mediates ischemia-reperfusion injury of the small intestine in adult mice.

Watanabe T, Tanigawa T, Kobata A, Takeda S, Nadatani Y, Otani K, Yamagami H, Shiba M, Tominaga K, Fujiwara Y, Arakawa T - PLoS ONE (2014)

Effect of TLR2 deficiency on the expression of inflammatory mediators, neutrophil infiltration, and prostaglandin E2 synthesis after the ischemia-reperfusion injury of the small intestine.Wild-type (WT) mice and TLR2 knockout mice were subjected to 45 min of ischemia, followed by 60 min of reperfusion. After removing the small intestine, the mRNA expression levels for the tumor necrosis factor (TNF)-α (A), the intercellular adhesion molecule (ICAM)-1 (B), and cyclooxygenase (COX)-2 (C) were determined. Assays were also performed to estimate the myeloperoxidase (MPO) activity (a marker of neutrophil infiltration, D), and the prostaglandin E2 concentrations (E). Each column represents the mean ± SD. N = 6. *P<0.01 vs WT mice with sham operation, #P<0.01 vs WT mice subjected to the ischemia-reperfusion injury. I/R; ischemia/reperfusion
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199713&req=5

pone-0110441-g002: Effect of TLR2 deficiency on the expression of inflammatory mediators, neutrophil infiltration, and prostaglandin E2 synthesis after the ischemia-reperfusion injury of the small intestine.Wild-type (WT) mice and TLR2 knockout mice were subjected to 45 min of ischemia, followed by 60 min of reperfusion. After removing the small intestine, the mRNA expression levels for the tumor necrosis factor (TNF)-α (A), the intercellular adhesion molecule (ICAM)-1 (B), and cyclooxygenase (COX)-2 (C) were determined. Assays were also performed to estimate the myeloperoxidase (MPO) activity (a marker of neutrophil infiltration, D), and the prostaglandin E2 concentrations (E). Each column represents the mean ± SD. N = 6. *P<0.01 vs WT mice with sham operation, #P<0.01 vs WT mice subjected to the ischemia-reperfusion injury. I/R; ischemia/reperfusion
Mentions: The intestinal I/R treatment increased expression levels of mRNAs for TNF-α, ICAM-1, and COX-2 in the small intestine of wild-type mice by 3.3-, 3.2-, and 13.0-fold, respectively (Figures 2A-2C). TLR2 deficiency prevented the I/R-induced increase in mRNAs for TNF-α and ICAM-1, but did not affect that in COX-2 mRNA. The I/R treatment also increased MPO activities in wild-type mice by 4.1-fold, but this effect was markedly inhibited in TLR2 KO mice (Figure 2D).

Bottom Line: Toll-like receptor 2 (TLR2) recognizes conserved molecular patterns associated with both gram-negative and gram-positive bacteria, and detects some endogenous ligands.TLR2 deficiency significantly inhibited the I/R-induced increase in MPO activity and the expression of mRNAs for TNF-α and ICAM-1, but did not affect the expression of COX-2 mRNA.TLR2 proteins were found to be expressed in the epithelial cells, inflammatory cells, and endothelial cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

ABSTRACT
Toll-like receptor 2 (TLR2) recognizes conserved molecular patterns associated with both gram-negative and gram-positive bacteria, and detects some endogenous ligands. Previous studies demonstrated that in ischemia-reperfusion (I/R) injury of the small intestine, the TLR2-dependent signaling exerted preventive effects on the damage in young mice, but did not have a significant effect in neonatal mice. We investigated the role of TLR2 in adult ischemia-reperfusion injury in the small intestine. Wild-type and TLR2 knockout mice at 16 weeks of age were subjected to intestinal I/R injury. Some wild-type mice received anti-Ly-6G antibodies to deplete circulating neutrophils. In wild-type mice, I/R induced severe small intestinal injury characterized by infiltration by inflammatory cells, disruption of the mucosal epithelium, and mucosal bleeding. Compared to wild-type mice, TLR2 knockout mice exhibited less severe mucosal injury induced by I/R, with a 35%, 33%, and 43% reduction in histological grading score and luminal concentration of hemoglobin, and the numbers of apoptotic epithelial cells, respectively. The I/R increased the activity of myeloperoxidase (MPO), a marker of neutrophil infiltration, and the levels of mRNA expression of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and cyclooxygenase-2 (COX-2) in the small intestine of the wild-type mice by 3.3-, 3.2-, and 13.0-fold, respectively. TLR2 deficiency significantly inhibited the I/R-induced increase in MPO activity and the expression of mRNAs for TNF-α and ICAM-1, but did not affect the expression of COX-2 mRNA. I/R also enhanced TLR2 mRNA expression by 2.9-fold. TLR2 proteins were found to be expressed in the epithelial cells, inflammatory cells, and endothelial cells. Neutrophil depletion prevented intestinal I/R injury in wild-type mice. These findings suggest that TLR2 may mediate I/R injury of the small intestine in adult mice via induction of inflammatory mediators such as TNF-α and ICAM-1.

Show MeSH
Related in: MedlinePlus