Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have evaluated the prostaglandin (PG) production and PG biosynthetic gene expression in a choriodecidual dispersed cell culture system. Cells dispersed from human choriodecidual membranes by dispase and trypsin digestion were evaluated after 1,3,5 and 7 days of culture for basal and tumour necrosis factor alpha (F-alpha) stimulated PGE2 production. The highest rates of production (P < 0.05) were obtained with cells treated after 3 days of culture, (3.7 +/- 1) x 10(2) pg PGE2 per 16 h per microg total cellular protein (mean +/- SEM), which was 3.9 times basal rate after 3 days culture. In choriodecidual cells treated after 3 days in culture, expression of prostaglandin endoperoxide H synthase-2 (PGHS-2) mRNAwas similarly responsive toTNF-alpha (3.9 times basal within 3 h of 30 ng/ml TNF-alpha) while there was little effect on PGHS-1 or cytosolic phospholipase A2 expression. Hence, the dispersed choriodecidual cell culture system described retainsTNF-alpha responsive PG biosynthetic capacity which is at least in part upregulated via increased expression of PGHS-2 mRNA.
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PMID:Regulation of prostaglandin biosynthesis in dispersed choriodecidual cells in culture. 1199 16

We have previously shown that mast cells enhance eosinophil survival and activation. In this study we further characterized mast cell activity toward eosinophils. Sonicate of both rat peritoneal mast cells and the human mast cell line 1 (HMC-1) induced a concentration-dependent IL-6 and IL-8 release from human peripheral blood eosinophils (ELISA). HMC-1-induced IL-8 release was significantly reduced by the tryptase inhibitors GW-45 and GW-58 (90 and 87%, respectively, at an optimal concentration) but not by anti-stem cell factor, anti-TNF-alpha, or anti-IFN-gamma neutralizing Abs or by the antihistamine drugs pyrilamine and cimetidine. In a manner similar to HMC-1, human recombinant tryptase induced the expression of mRNA for IL-8 (RT-PCR) and caused IL-8 release from the eosinophils. Addition of cycloheximide, actinomycin D, dexamethasone, PD 98059, curcumin, or SB 202190 completely inhibited the tryptase-induced IL-6 and IL-8 release. In contrast, cyclosporin A had no effect on tryptase-induced IL-8 release. Tryptase caused phosphorylation of extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinases 1 and 2, and p38 (Western blot). Tryptase also induced the translocation of c-Jun from the cytosol to the nucleus (confocal microscopy) and enhanced AP-1 binding activity to the DNA (EMSA). Eosinophils were found to express proteinase-activated receptor 2 (FACS). When eosinophils were incubated with tryptase in the presence of anti-proteinase-activated receptor 2 antagonist Abs a significant decrease in the IL-6 and IL-8 release occurred. In summary, we have demonstrated that the preformed mast cell mediator tryptase induces cytokine production and release in human peripheral blood eosinophils by the mitogen-activated protein kinase/AP-1 pathway.
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PMID:Tryptase activates the mitogen-activated protein kinase/activator protein-1 pathway in human peripheral blood eosinophils, causing cytokine production and release. 1219 39

Proteinase-activated receptor 2 (PAR2) is cleaved and activated by trypsin or mast cell tryptase, and may play an important role in inflammation. We have investigated the potential of PAR2 agonists to modulate TNF-alpha secretion from human astrocytoma cell line CCF-STTG1. We found that CCF-STTG1 expresses PAR2 by RT-PCR and Western blot analysis. Agonists such as trypsin, the peptide SLIGKV-NH(2) (corresponding to the PAR2 tethered ligand), or mast cell tryptase directly signal to CCF-STTG1 to stimulate secretion of TNF-alpha but do not stimulate in the presence of soybean trypsin inhibitor (SBTI) or VKGILS-NH(2) (reverse peptide). The secretion of TNF-alpha by trypsin was significantly blocked by pretreatment with either 50 microM PD98059 or 1 microM SB203580. Furthermore, trypsin stimulated the activation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase homologue in CCF-STTG1 without any detectable activation of c-Jun N-terminal kinase (JNK). These results show that trypsin may induce TNF-alpha secretion following activation of ERK and p38 via PAR2 in CCF-STTG1.
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PMID:Agonists of proteinase-activated receptor 2 induce TNF-alpha secretion from astrocytoma cells. 1241 69

This study was undertaken to investigate the molecular constituents mediating LS174T colon adenocarcinoma cell adhesion to 4-h TNF-alpha-stimulated human umbilical vein endothelial cells (HUVECs) under flow. At 1 dyn/cm(2), approximately 57% of cells rolled and then became firmly adherent, whereas others continuously rolled on endothelium. Initial cell binding was primarily mediated by endothelial E-selectin. By using neuraminidase, glycolipid biosynthesis inhibitor d,l-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol. HCl, trypsin, and flow cytometry, LS174T cells were shown to express sialyl Lewis(x) (sLe(x))- and di-sLe(x)-decorated, but not sLe(a)-decorated, glycolipid and glycoprotein ligands for E-selectin. The cells preferentially employed sialylated glycoproteins over glycolipids in adhesion as measured by conversion of rolling to firm adhesion, resistance to detachment by increased shear stress, and rolling velocity. However, a nonsialylated E-selectin counterreceptor also exists. Furthermore, LS174T alpha(2), alpha(6), and beta(1) integrins support a minor pathway in adhesion to HUVECs. Finally, tumor cell attachment specifically increases HUVEC endocytosis of E-selectin. Altogether, the data indicate the complexity of carcinoma cell-endothelium adhesion via sialylated glycoconjugates, integrins, and their respective counterreceptors.
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PMID:Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow. 1247 67

Treatments for pancreatitis are limited. Activation of transcription factor NF-kappaB, a key regulator of inflammatory molecule expression, is an early event in experimental pancreatitis and correlates with the inflammatory response. We report here that curcumin, a natural phytochemical known to inhibit NF-kappaB and activator protein (AP)-1, another important proinflammatory transcription factor, ameliorates pancreatitis in two rat models. In both cerulein pancreatitis and pancreatitis induced by a combination of ethanol diet and low-dose CCK, curcumin improved the severity of the disease as measured by a number of parameters (histology, serum amylase, pancreatic trypsin, and neutrophil infiltration). Curcumin markedly inhibited NF-kappaB and AP-1 activation, assessed by DNA binding and degradation of inhibitory IkappaB proteins, and the induction of mRNAs for cytokines IL-6 and TNF-alpha, the chemokine KC, and inducible nitric oxide synthase in pancreas. Curcumin also blocked CCK-induced NF-kappaB and AP-1 activation in isolated pancreatic acini. Our findings indicate that blocking key signals of the inflammatory response ameliorates pancreatitis in both ethanol and nonethanol models. They suggest that curcumin, which is currently in clinical trials for cancer prevention, may be useful for treatment of pancreatitis.
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PMID:Curcumin ameliorates ethanol and nonethanol experimental pancreatitis. 1248 37

Fexofenadine is a non-sedating selective third-generation antihistamine, which also exerts an anti-inflammatory action. The aim of this study was to evaluate the influence on the expression of inflammatory skin mediators, together with the efficacy and tolerability, of fexofenadine in chronic idiopathic urticaria (CIU). Fexofenadine 180mg was administered once daily for 4 weeks after a placebo run-in phase of 3 to 7 days. Efficacy paramaters were obtained from patients' assessment of urticaria symptoms. Non-lesional skin of patients with active CIU was studied immunohistochemically before and after treatment. The expression of the following mediators was evaluated: adhesion molecules (ICAM-1, ELAM-1, VCAM-1); mast cell proteases (chymase and tryptase) and proinflammatory cytokines (IL-1beta, IL-3, IL-6 and TNF-alpha). Of the 20 subjects enrolled, 3 dropped out of the study. Treatment proved successful in most cases (88.2%) (p <0.01) and a significant improvement of all symptoms was registered. Treatment was well-tolerated by all patients; adverse events, neither serious nor drug-related, occurred in any case. Immunochemistry revealed at the baseline a significant expression of ELAM-1, VCAM-1, tryptase, chymase, and TNF-alpha (p= 0.05) in non-lesional skin of patients compared to normal controls. After treatment with fexofenadine, there was a significant decrease in the expression of ELAM-1 (p= 0.02), VCAM-1 (p= 0.04) and tryptase (p= 0.04), whereas no relevant change was observed for the other parameters examined. This work confirms the efficacy and tolerability of fexofenadine HCl 180mg in CIU. These preliminary data show a trend towards a decrease in the expression of tryptase and some adhesion molecules after treatment, suggesting an anti-inflammatory activity of fexofenadine.
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PMID:Fexofenadine in chronic idiopathic urticaria: a clinical and immunohistochemical evaluation. 1257 22

A new pimarane-type diterpene compound, acanthokoreoic acid A together with three known compounds, acanthoic acid, acanthol, and sumogaside were isolated from a CH(2)Cl(2) fraction of Acanthopanax koreanum by repeated column chromatography and reversed phase preparative HPLC. Acanthoic acid was isolated in high yields and showed potent inhibitory activity on the IL-8 secretion of the TNF-alpha-stimulated human colon adenocarcinoma cell line HT-29 and on the TNF-alpha secretion of the trypsin-stimulated human leukemic mast cell line HMC-1.
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PMID:Inhibitory effect of TNF-alpha and IL-8 secretion by pimarane-type diterpenoids from Acanthopanax koreanum. 1273 67

Trypsin activating both proteinase-activated receptor (PAR) 2 and PAR4 plays an important role in inflammation. We have investigated the potential of trypsin to induce TNF-alpha secretion from the human leukemic mast cell line (HMC-1). HMC-1 cells co-express both PAR2 and PAR4, and their agonist trypsin signals to HMC-1 cells. Trypsin (100 nm), SLIGKV-NH(2) (100 microm, corresponding to the PAR2 tethered ligand), or GYPGQV-NH(2) (100 microm, corresponding to the PAR4 tethered ligand) induced tumour necrosis factor (TNF)-alpha secretion from HMC-1 cells. TNF-alpha secretion by trypsin was significantly blocked by pretreatment with 50 microm PD098059, MEK-1 inhibitor. Furthermore, trypsin stimulated the activation of extracellular signal-regulated kinase (ERK) in HMC-1 cells without any detectable activation of c-Jun N-terminal kinase (JNK) and p38 MAP kinase homologue. These results show that trypsin may induce TNF-alpha secretion following activation of ERK via both PAR2 and PAR4 on HMC-1 cells.
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PMID:Trypsin induces tumour necrosis factor-alpha secretion from a human leukemic mast cell line. 1273 6

Although tryptase released from mast cells might play a key role in the pathogenesis of ulcerative colitis (UC), the role of protease-activated receptor 2 (PAR2), tryptase receptor, remains unclear in the pathogenesis of this disease. The expressions of PAR2 and tumor necrosis factor (TNF) alpha in nine UC tissues and nine normal tissues were examined by immunohistochemistry. TNF-alpha levels secreted from human leukemic mast cell line (HMC-1) after the treatment of PAR2 agonists were also measured by enzyme-linked immunosorbent assay. The PAR2 and TNF-alpha proteins were more significantly detectable in UC tissues than in normal tissues. Furthermore, 65.2% of PAR2+ cells and 66.4% of TNF-alpha+ cells in UC tissues were tryptase-positive cells. In other words, 60.6% and 46.3% of tryptase-positive cells in UC tissues were PAR2+ cells and TNF-alpha+ cells, respectively. A chi2 analysis showed correlation (p < 0.007) between PAR2 and TNF-alpha in tryptase-positive mast cells. Moreover, PAR2 agonists significantly induced the TNF-alpha secretion from HMC-1. These results indicate that the activation of the mast cells through PAR2 may be involved in the pathogenesis of UC.
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PMID:Expression of protease-activated receptor 2 in ulcerative colitis. 1290 45

Five known kaurane type diterpenoids, 16alphaH,17-isovaleryloxy-ent-kauran-19-oic acid (1), 16alpha-hydroxy-17-isovaleryloxy-ent-kauran-19-oic acid (2), paniculoside-IV (3), 16alpha-hydroxy-ent-kauran-19-oic acid (4), and ent-kaur-16-en-19-oic acid (5) were isolated from the root of Acanthopanax koreanum by repeated column chromatography and reversed phase preparative HPLC. The structures of these compounds were established from physicochemical and spectral data. Among the isolated compounds 16alphaH,17-isovaleryloxy-ent-kauran-19-oic acid (1) showed potent inhibitory activity (IC50 value, 16.2 uM) on TNF-alpha secretion from HMC-1, a trypsin-stimulated human leukemic mast cell line.
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PMID:Inhibitory effect of kaurane type diterpenoids from Acanthopanax koreanum on TNF-alpha secretion from trypsin-stimulated HMC-1 cells. 1456 Sep 22


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