Expression of PAR2 in portal vein cancer embolus and hepatocellular carcinoma / 重庆医学

Objective To investigate the expression of proteinase active receptor 2(PAR2)protein in hepatocellular carcino-ma(HCC)and portal vessel tumor thrombosis(PVTT)to evaluate its clinical value.Methods Immunofluorescence,RT-PCR and Western blot were used to examine the expression of PAR2 protein in cancer tissue,tumor thrombosis and cancer-adjacent normal tissue from 21 patients with HCC.Results The expression pattern of PAR2 protein was different cancer tissue and cancer-adjacent normal tissue.PAR2 labeling index was significantly higher in cancer tissue and PVTT than cancer-adjacent normal tissue(P 0.05).Conclusion PAR2 is over-expressed in HCC and PVTT.PAR2 expression is re-lated with the development and progression of HCC.

Epidermal Proteinase-Activated Receptor-2 Expression is Increased in End-Stage Renal Disease Patients with Pruritus: A Pilot Study

Uremic pruritus is a common problem in patients with end-stage renal disease (ESRD), but the underlying mechanisms are not yet fully understood. We aimed to investigate the association between severity of uremic pruritus and cutaneous serine protease activity, as well as proteinase-activated receptor-2 (PAR-2) expression. Twelve ESRD patients with pruritus, 4 ESRD patients without pruritus, and 6 healthy controls were enrolled. Skin biopsies were obtained from the abdomen. Protease activity and PAR-2 expression in the epidermis were examined by in situ zymography and confocal laser microscopy, respectively. All ESRD patients presented more pronounced cutaneous protease activity compared with that in healthy controls. The skin samples from the patients with pruritus showed higher protease activity than either nonpruritic ESRD patients or healthy controls. The epidermis in all samples of ESRD patients presented higher immunoreactivity against PAR-2 versus those of healthy controls. In addition, correlation analysis between PAR-2 expression and VAS pruritus scores showed a significant positive correlation. Our data suggests that levels of serine protease and PAR-2 expression could play important roles in the pathogenesis of uremic pruritus.

Effect of Protease Activated Receptor-2 Agonist on Intestinal SIgA in Rats with Acute Necrotizing Pancreatitis / 医药导报

Objective To discuss the effects of proteinase-activated receptor-2( PAR-2 )agonists on intestinal SIgA levels in rats with severe acute necrotizing pancreatitis( SAP). Methods This study established SAP rat model and observed the levels of TNF-α and IL-6 in intestinal mucosa,SIgA content in intestinal mucus and histopathological changes of intestinal mucosa 6,12,and 24 h after establishment of model. The univariate analysis was used to compare the difference among groups. Linear correlation analysis was used to compare correlation between inflammatory mediators( TNF-α,IL-6 )and SIgA content in intestinal mucus,as well as the histopathological scores of intestinal mucosa. Results The level of TNF-α and IL-6 in intestinal mucosa and histopathological scores of intestinal mucosa were all significantly increased but SIgA content was decreased in model group at each time point after establishment of model,as compared with the sham-operated group(P﹤0. 05). The level of TNF-α and IL-6 in intestinal mucosa and histopathological scores of intestinal mucosa were all significantly decreased while SIgA content in intestinal mucus increased in pretreatment group at each time point after establishment of model,as compared with the model group(P﹤0. 05). There was a positive relationship between inflammatory mediators(TNF-α,IL-6)in intestinal mucosa and histopathological scores of intestinal mucosa(P﹤0. 01). There was a negative relationship between inflammatory mediators(TNF-α,IL-6)and SIgA content in intestinal mucus(P﹤0. 05). Conclusion Intestinal mucosa immune barrier was impaired in the early stage of SAP in rats. PAR-2 agonist has therapeutic effects on intestinal mucosa immune barrier,which is related to the inhibition of excessive release of inflammatory mediators( TNF-α and IL-6)in rats with SAP.

Effect of Pertussis Toxin and Herbimycin A on Proteinase-Activated Receptor 2-Mediated Cyclooxygenase 2 Expression in Helicobacter pylori-Infected Gastric Epithelial AGS Cells

Helicobacter pylori (H. pylori) is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. Proteinase-activated receptor 2 (PAR2), subgroup of G-protein coupled receptor family, is highly expressed in gastric cancer, and chronic expression of cyclooxygenase-2 (COX-2) plays an important role in H. pylori-associated gastric carcinogenesis and inflammation. We previously demonstrated that H. pylori induced the expression of PAR2 and COX-2 in gastric epithelial cells. Present study aims to investigate whether COX-2 expression induced by H. pylori in Korean isolates is mediated by PAR2 via activation of Gi protein and Src kinase in gastric epithelial AGS cells. Results showed that H. pylori-induced COX-2 expression was inhibited in the cells transfected with antisense oligonucleotide for PAR2 or treated with Gi protein blocker pertussis toxin, Src kinase inhibitor herbimycin A and soybean trypsin inbitor, indicating that COX-2 expression is mediated by PAR2 through activation of Gi protein and Src kinase in gastric epithelial cells infected with H. pylori in Korean isolates. Thus, targeting the activation of PAR2 may be beneficial for prevention or treatment of gastric inflammation and carcinogenesis associated with H. pylori infection.

Relationship between mast cells and renal interstitial fibrosis in interstitial nephritis / 中华肾脏病杂志

Objective To explore the potential relationship between tryplase-positive mast cells (MCs) infiltration and renal interstitial fibrosis in acute interstitial nephritis (AIN) and chronic interstitial nephritis (CIN). Methods Renal biopsy specimens from patients with AIN (n=11) and CIN (n=16) were studied and 11 patients in minimal change diseases (MM)were as controls. Histochemistry and immunohistochemistry staining assay were applied to delect the expression of tryptase, proteinase-activated receptor-2 (PAR-2), TGF-?1 and collagen type I (Col I )in the renal tissues. Immunofluo-rescence double-staining assay was used to assess the relationship among MCs, PAR-2-positive cells, and TGF-?1-positive cells in the renal interstitium respectively. Results MCs in AIN and CIN were significantly increased compared with those in controls and were mainly scattered in the fibrotic areas of renal interstitium. The relative immunostaining areas for PAR-2, TGF-?1 in the renal tubular epithelial cells (RTECs) and Col I were significantly larger in AIN and CIN than those in controls respectively (P

Proteinase activated receptor-2 promotes IL-4 release from mast cells / 中国免疫学杂志

Objective:To investigate the effect of activation of proteinase activated receptor(PAR)2 on mediator release from mast cells.Methods:P815 cells(a mast cell line) were challenged with various concentrations of PAR-2 agonist peptide,trypsin,tryptase or elasetase with or without PAR-2 antagonist peptide.The supernatants were collected and analyzed by enzyme-linked immunosorbent assay(ELISA) to detect the quantity of released IL-4,IL-6 and histamine.Results:PAR-2 agonist peptide,trypsin or tryptase induced a concentration-dependent IL-4,but not histamine release from P815 mast cells.Trypsin and tryptase induced IL-4 release from the mast cells was blocked by addition of PAR-2 antagonist peptide.No IL-4,IL-6 and histamine release was observed when P815 cells were incubated with elasetase.Conclusion:Induction of IL-4 release from mast cells by trypsin and tryptase through activation of PAR-2 added some novel information on the hypothesis of self-amplification mechanism of mast cell activation.