Proinflammatory role of protease-activated receptor-2 in intestinal ischemia/reperfusion injury in rats

Abstract

Abstract. Protease-activated receptors (Pars) are widely recognized for their modulatory properties during inflammation. The aim of the present study was to examine the role of Par-2 on ischemia/reperfusion-induced small intestinal injury in rats. intestinal damage was induced in male Wistar rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion for 60 min. expression of Par-2 in the intestinal mucosa was estimated by Western blot analysis and real-time Pcr. anti-rat Par-2 cleavage site (PcS) antibody was intraperitoneally administered to the rats 1 h before the vascular clamping. The intestinal mucosal injury and inflammation were evaluated by biochemical markers and histological findings. Thiobarbituric acid (TBa) reactive substances and tissueassociated myeloperoxidase (MPo) activity were measured in the intestinal mucosa as indices of lipid peroxidation and neutrophil infiltration, respectively. Expression of cytokineinduced neutrophil chemoattractant-1 (cinc-1) in intestinal mucosa was measured by enzyme-linked immunosorbent assay. expression of Par-2 mrna and protein in the intestinal mucosa was increased after reperfusion following ischemia. reperfusion after ischemia resulted in an increase in luminal protein concentrations, hemoglobin concentrations, TBa reactive substances, MPo activity and cinc-1 protein.Pre-treatment with anti-rat PCS antibody significantly inhibited the increases in these parameters. These results suggest that Par-2 plays an important role in the pathogenesis of ischemia/reperfusion-induced intestinal injury.

Retraction: Asiatic Acid from <i>Potentilla chinensis</i> Attenuate Ethanol-Induced Hepatic Injury <i>via</i> Suppression of Oxidative Stress and Kupffer Cell Activation

“…Liver Myeloperoxidase Activity Assays Myeloperoxidase (MPO) activity was measured according to the method of Yoshida et al 22) Tissue was homogenized in 50 mM phosphate buffer (pH 6.0) containing 0.5% hexadecyltrimethylammonium bromide. The supernatant remaining after centrifugation was then mixed with 10 mM phosphate buffer (pH 6.0) and 1 mL of 1.5 mM o-dianisidine hydrochloride containing 0.2 mM H 2 O 2 .…”

Mast-Cell-Releasing Tryptase Triggers Acute Lung Injury Induced by Small Intestinal Ischemia–Reperfusion by Activating PAR-2 in Rats

“…A very recent study revealed that PAR-2 participates in small intestinal ischemia-reperfusion by observing the protective effects against reperfusion injury using PAR-2 antibody [31], and other publications have supported that PAR-2 plays an important role in acute lung injury [32,33]; therefore, in present study, we did not choose the agent to inhibit PAR-2 to observe the precise role in lung injury.…”

Inhibition of coagulation proteases Xa and IIa decreases ischemia–reperfusion injuries in a preclinical renal transplantation model

“…6 Indeed, Xa and IIa cleave the protease-activated receptors (PAR) which subsequently induce the production of vascular adhesion, proinflammatory and pro-fibrotic molecules. 7 It was demonstrated that PAR-1 and PAR-2 activated by coagulation proteases, play a crucial role in IRI, 8,9 in association with fibrosis, tissue remodeling and inflammation. 10,11 As a consequence, the coagulation cascade is one major target to limit IRI.…”