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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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Expression of TLR2 during the development of the intestinal ischemia-reperfusion injury.Wild-type mice were subjected to 45 min of ischemia followed by 60 min of reperfusion. After removal of the small intestine, expression of TLR2 was examined by real-time RT-PCR and immunohistochemical staining. (A) Effect of the ischemia/reperfusion (I/R) treatment on intestinal TLR2 mRNA. Each column represents the mean ± SD. N = 6. *P<0.01 vs mice with sham operation. (B, C) Immunohistochemical staining for TLR2. TLR2 proteins were expressed in epithelial cells, inflammatory cells (arrow heads), and endothelial cells (arrows) in the injured small intestine.
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pone-0110441-g004: Expression of TLR2 during the development of the intestinal ischemia-reperfusion injury.Wild-type mice were subjected to 45 min of ischemia followed by 60 min of reperfusion. After removal of the small intestine, expression of TLR2 was examined by real-time RT-PCR and immunohistochemical staining. (A) Effect of the ischemia/reperfusion (I/R) treatment on intestinal TLR2 mRNA. Each column represents the mean ± SD. N = 6. *P<0.01 vs mice with sham operation. (B, C) Immunohistochemical staining for TLR2. TLR2 proteins were expressed in epithelial cells, inflammatory cells (arrow heads), and endothelial cells (arrows) in the injured small intestine.

Mentions: The I/R treatment enhanced TLR2 mRNA expression by 2.9-fold (Figure 4A). Upon immunohistochemical examination, TLR2 proteins were found to be expressed in epithelial cells, inflammatory cells, and endothelial cells in the injured small intestine (Figures 4B and 4C).


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)

Expression of TLR2 during the development of the intestinal ischemia-reperfusion injury.Wild-type mice were subjected to 45 min of ischemia followed by 60 min of reperfusion. After removal of the small intestine, expression of TLR2 was examined by real-time RT-PCR and immunohistochemical staining. (A) Effect of the ischemia/reperfusion (I/R) treatment on intestinal TLR2 mRNA. Each column represents the mean ± SD. N = 6. *P<0.01 vs mice with sham operation. (B, C) Immunohistochemical staining for TLR2. TLR2 proteins were expressed in epithelial cells, inflammatory cells (arrow heads), and endothelial cells (arrows) in the injured small intestine.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0110441-g004: Expression of TLR2 during the development of the intestinal ischemia-reperfusion injury.Wild-type mice were subjected to 45 min of ischemia followed by 60 min of reperfusion. After removal of the small intestine, expression of TLR2 was examined by real-time RT-PCR and immunohistochemical staining. (A) Effect of the ischemia/reperfusion (I/R) treatment on intestinal TLR2 mRNA. Each column represents the mean ± SD. N = 6. *P<0.01 vs mice with sham operation. (B, C) Immunohistochemical staining for TLR2. TLR2 proteins were expressed in epithelial cells, inflammatory cells (arrow heads), and endothelial cells (arrows) in the injured small intestine.
Mentions: The I/R treatment enhanced TLR2 mRNA expression by 2.9-fold (Figure 4A). Upon immunohistochemical examination, TLR2 proteins were found to be expressed in epithelial cells, inflammatory cells, and endothelial cells in the injured small intestine (Figures 4B and 4C).

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