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)

The effects of lamina propria mononuclear cell culture supernatant on epithelial cell DNA synthesis were studied using cells isolated from patients with inflammatory bowel disease and normal controls. Supernatants from resting and phytohaemagglutinin stimulated cells were studied and supernatants that strongly promoted DNA synthesis were pooled, and growth factor activity partially characterised. The effects of recombinant interleukins-1 beta,2,3,interferon-gamma, and granulocyte macrophage colony stimulating factor were tested in the same system. Resting lamina propria mononuclear cells produce factors that increase DNA synthesis. Production of these factors is increased by phytohaemagglutinin stimulation. No significant differences were found in production of these factors between patients with inflammatory bowel disease and normal controls. The molecular weight of the active factor(s) lies in the region 31-48 kD. Chromatofocusing produced two peaks of activity, one in the region pk 5.5 and one around pk 6.4. The activity was heat and acid pH labile. Activity was not destroyed, however, by 0.05% trypsin. Recombinant granulocyte macrophage colony stimulating factor was a weak stimulus to epithelial DNA synthesis, interleukin-1 beta was weakly inhibitory but other cytokines tested did not have any effect. Granulocyte macrophage colony stimulating factor is probably important in controlling epithelial cell growth.
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PMID:Production of epithelial cell growth factors by lamina propria mononuclear cells. 174 Feb 74

The presence of antibodies against pancreatic juice (PAB) in patients with Crohn's disease has recently been reported. In our study sera from 273 patients with inflammatory bowel disease (222 with Crohn's disease, 51 with ulcerative colitis) have been examined for PAB and also for antibodies against gut tissues by means of indirect immunofluorescence. PAB were found in 68 of the 222 patients with Crohn's disease (31%), with titres ranging from 1/10 to 1/1280, and in only two patients with ulcerative colitis (4%), with titres of 1/20. None were found in 198 patients with various chronic inflammatory diseases and healthy control subjects. No differences were found between the PAB positive and negative patients when the following parameters were compared: disease activity (Crohn's disease activity index), involvement of bowel segments, incidence of extraintestinal disease, or treatment with anti-inflammatory drugs. Only seven of the patients with Crohn's disease had a history of pancreatic disease and of these, four had detectable pancreatic antibodies. Longitudinal observations of 40 patients with Crohn's disease showed a stable pattern for PAB, independent of disease activity and treatment. Partial characterisation of the PAB antigen, isolated from pancreatic juice, showed a trypsin sensitive macromolecular protein of more than 10(6) daltons not identical with a panel of defined exocrine pancreatic proteins. By contrast, antibodies against goblet cells (GAB) were found in 13 of 51 patients with ulcerative colitis (29%) and in none of the patients with Crohn's disease or control subjects. PAB were found as a highly specific serological marker for Crohn's disease and GAB for ulcerative colitis, but the relevance of PAB and GAB in the pathogenesis in Crohn's disease remains unclear.
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PMID:Antibodies to a trypsin sensitive pancreatic antigen in chronic inflammatory bowel disease: specific markers for a subgroup of patients with Crohn's disease. 195 75

Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and increased gut permeability and may be responsible for some of the symptoms and signs of inflammatory bowel disease. We have used a novel monoclonal antibody (AAI) against tryptase expressed exclusively in the granules of mast cells to enumerate mast cells in rectal biopsies in order to study the effect of inflammatory bowel disease and drug treatment upon rectal mast cell numbers. Rectal mast cell numbers are significantly reduced in inflammatory bowel disease patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control patients (10.1, P less than 0.001) and inflammatory bowel disease patients not taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The reduction in mast cell counts was independent of the degree of inflammation or architectural distortion. There was a negative correlation between the dose of corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank correlation), and the mast cell count was reduced within a few days of treatment and remained low throughout steroid therapy. Mucosal mast cell depletion may be an important mechanism of action of corticosteroids in inflammatory bowel disease.
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PMID:Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease. 197 67

The function of human purified colostral and gastrointestinal IgA has been studied by its ability to agglutinate common gastrointestinal organisms. Agglutinating activity was unaffected by trypsin or acid but it was abolished rapidly by pepsin. Both colostral and gastrointestinal IgA agglutinated a wide range of enteric organisms. Variations in this activity occurred between different individuals, and between different gastrointestinal sites in the same individual. In preliminary studies, saliva and IgA prepared from gastric and jejunal secretions in patients with pernicious anaemia showed a more uniform agglutination pattern than IgA prepared from the same sites in other patients. The agglutinin activity of IgA prepared from a particular site may be determined by the bacterial flora at that site. Agglutination methods for assessing the function of gastrointestinal antibody may be of value in the study of the possible roles of antibodies in inflammatory bowel disease.
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PMID:Bacterial agglutination studies with secretory IgA prepared from human gastrointestinal secretions and colostrum. 455 7

Elevated serum and urine amylase and serum lipase values are not always diagnostic of an acute pancreatitis, on the account of the extrapancreatic production of these enzymes. A diagnostic improvement can be made by using the CAm/CCr ratio, but this index too is abnormal in some non pancreatic diseases. Since trypsin measurement seems to be more specific in the evaluation of pancreatic condition, serum trypsin-like immunoreactivity has been measured in 28 patients with acute pancreatitis, 95 patients with a wide spectrum of gastroenterological diseases and in 30 patients with severe chronic renal failure. 85 normal subjects were used as controls. Abnormally high serum trypsin-like immunoreactivity (TLI) values were detected in 100% of patients with acute pancreatitis, without any overlap with normal controls. TLI values above the upper normal limit were also found in 70% of patients with severe renal damage, while none of the patients with liver disease, biliary disease, peptic ulcer an inflammatory bowel disease had elevated TLI levels. In 29 patients with hyperamylasemia due to extra-pancreatic diseases serum trypsin-like immunoreactivity was always within the normal range. It is concluded that the determination of serum TLI is a sensitive and reliable tool in the diagnosis of an acute pancreatic inflammation, providing that a severe renal failure is excluded.
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PMID:Trypsin-like immunoreactivity in the diagnosis of acute pancreatitis. 616 10

Previous studies on the frequency of intestinal mast cells and eosinophils in patients with inflammatory bowel disease yielded conflicting results. In the present morphometric study, we quantified mast cells and eosinophils in the lamina propria by histological and immunohistochemical methods in 64 patients suffering from Crohn's disease (33 cases) or ulcerative colitis (31 cases), and in 29 controls. Histological data from 206 biopsies were related to the presence of mucosal inflammation and clinical parameters. The number of eosinophils was increased in patients with inflammatory bowel conditions (mean +/- SE: 331 +/- 44/mm2) as compared to controls (258 +/- 27/mm2), and was dependent on disease activity and drug treatment. Mean mast cell numbers did not differ between patients and controls. However, a reduced mast cell number was found in toluidine blue-stained sections of actively inflamed tissue areas (143 +/- 16/mm2, versus 206 +/- 18/mm2 in non-inflamed tissue). Immunohistochemical studies using antibodies against the granule proteins tryptase and chymase suggest that this decrease in mast cell numbers is due to mast cell degranulation. The present data show that the number of intestinal mast cells and eosinophils is altered in patients with inflammatory bowel diseases, suggesting that both cell types are involved in the pathogenesis of chronic intestinal inflammation.
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PMID:Quantitative assessment of intestinal eosinophils and mast cells in inflammatory bowel disease. 883 15

C3H/HeJBir mice are a new substrain that spontaneously develop colitis early in life. This study was done to determine the T cell reactivity of C3H/HeJBir mice to candidate antigens that might be involved in their disease. C3H/HeJBir CD4+ T cells were strongly reactive to antigens of the enteric bacterial flora, but not to epithelial or food antigens. The stimulatory material in the enteric bacteria was trypsin sensitive and restricted by class II major histocompatibility complex molecules, but did not have the properties of a superantigen. The precursor frequency of interleuken (IL)-2-producing, bacterial-reactive CD4+ T cells in colitic mice was 1 out of 2,000 compared to 1 out of 20,000-25,000 in noncolitic control mice. These T cells produced predominately IL-2 and interferon gamma, consistent with a T helper type 1 cell response and were present at 3-4 wk, the age of onset of the colitis. Adoptive transfer of bacterial-antigen-activated CD4+ T cells from colitic C3H/HeJBir but not from control C3H/HeJ mice into C3H/HeSnJ scid/scid recipients induced colitis. These data represent a direct demonstration that T cells reactive with conventional antigens of the enteric bacterial flora can mediate chronic inflammatory bowel disease.
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PMID:CD4+ T cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice: increased T helper cell type 1 response and ability to transfer disease. 950 Jul 88

Tryptases are serine proteases involved in mast cell-mediated inflammatory responses which represent potential targets of drugs against diseases such as asthma, arthritis and inflammatory bowel disease. In order to interpret pharmacodynamic data on the tryptase inhibitors undergoing clinical trials, we defined the genetic variability of the tryptase 1 (TPS1) and tryptase 2 (TPS2) loci by screening a reference population of 32 individuals representing three major ethnic groups (Caucasian, African American, Asian). Using overlapping PCR products, we resequenced the entire tryptase genes with the only exclusion of TPS2 intron 1 and 20 bp of TPS2 5' untranslated region included in exon 1 and we identified 21 novel single nucleotide polymorphisms in TPS1 and 17 single nucleotide polymorphisms plus a large polymorphic deletion in the TPS2 gene. We also compared the type, frequency and distribution of single nucleotide polymorphisms in TPS1 and TPS2 and we observed that the polymorphism frequency within these two loci is unexpectedly high (approximately 1 SNP every 90 bp) and that some of the allele frequencies differ significantly among the three ethnic groups. Based on differences observed in preclinical studies using a cynomolgus monkey (Macaca fascicularis) asthma model system, we investigated the difference between monkey and human tryptase genes in order to better understand the mechanism of action of our tryptase inhibitors.
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PMID:Characterization of two highly polymorphic human tryptase loci and comparison with a newly discovered monkey tryptase ortholog. 1089 8

Proteinases are important at several phases of physiological and pathological inflammation, mediating cellular infiltration, cytokine activation, tissue damage, remodeling, and repair. However, little is known of their role in the pathogenesis of inflammatory bowel disease. The aim of this study was to assess the role of tissue proteases in a mouse model of colitis. Proteolytic activity was analyzed, using gel and in situ zymography, in colonic tissues from severe combined immunodeficient mice with colitis induced by transfer of CD4(+) T lymphocytes. Serine proteinase levels increased in colitic tissue, with major species of 23 kd, 30 kd, and 45 kd. Co-migration and inhibition studies indicated that the 23-kd proteinase was pancreatic trypsin and that the 30-kd species was neutrophil elastase. Matrix metalloproteinase (MMP)-9 expression, and MMP-2 and MMP-9 activation, was elevated in colitic tissues. Proteinase levels followed a decreasing concentration gradient from proximal to distal colon. Proteolysis was localized to infiltrating leukocytes in diseased severe combined immunodeficient mice. Transmural inflammation was associated with serine proteinase and MMP activity in overlying epithelium and with marked subepithelial proteolytic activity. The results demonstrate a clear elevation in the levels and activation of proteases in colitis, potentially contributing to disease progression through loss of epithelial barrier function.
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PMID:The role of up-regulated serine proteases and matrix metalloproteinases in the pathogenesis of a murine model of colitis. 1110 65

Proteinase-activated receptor (PAR) type 2 (PAR-2) has been shown to mediate ion secretion in cultured epithelial cells and rat jejunum. With the use of a microUssing chamber, we demonstrate the role of PAR-2 for ion transport in native human colonic mucosa obtained from 30 normal individuals and 11 cystic fibrosis (CF) patients. Trypsin induced Cl(-) secretion when added to the basolateral but not luminal side of normal epithelia. Activation of Cl(-) secretion by trypsin was inhibited by indomethacin and was further increased by cAMP in normal tissues but was not present in CF colon, indicating the requirement of luminal CF transmembrane conductance regulator. Effects of trypsin were largely reduced by low Cl(-), by basolateral bumetanide, and in the presence of barium or clotrimazole, but not by tetrodotoxin. Furthermore, trypsin-induced secretion was inhibited by the Ca(2+)-ATPase inhibitor cyclopiazonic acid and in low-Ca(2+) buffer. The effects of trypsin were almost abolished by trypsin inhibitor. Thrombin, an activator of PAR types 1, 3, and 4, had no effects on equivalent short-circuit currents. The presence of PAR-2 in human colon epithelium was confirmed by RT-PCR and additional experiments with PAR-2-activating peptide. PAR-2-mediated intestinal electrolyte secretion by release of mast cell tryptase and potentiation of PAR-2 expression by tumor necrosis factor-alpha may contribute to the hypersecretion observed in inflammatory processes such as chronic inflammatory bowel disease.
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PMID:Activation of ion secretion via proteinase-activated receptor-2 in human colon. 1180 40


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