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)

Chronic ulcerative colitis (CUC) is an inflammatory destructive disease of the large intestine characterized by motility and secretion disorders. In the past decade, attention has been paid to the role of neuronal structures and mast cells in regulating inflammatory and immune responses in inflammatory bowel disease (IBD). The present study was performed to demonstrate neuronal fibres (NF) and cells containing substance P (SP), tryptase and serotonin (SER) in the colonic wall of patients with CUC in remission. Biopsy specimens of 6 patients with CUC were investigated with immunocytochemical methods. Normal colon tissue obtained from 6 patients with rectal carcinoma was used as a control. An increased number of SP- and SER-positive NF was found in all the layers of the intestinal wall. The number of SER-containing endocrine cells in the mucosal glands was also increased per crypt. Tryptase-, SP- and SER-immunopositive mast cells were found in higher amounts than in control specimens in close apposition to the basal lamina of the glands among the epithelial cells and in other layers of the gut wall. Two types of mast cells were found: mast cells containing both tryptase and SP, and mast cells containing tryptase only. It is concluded that interactions between neuronal elements and mast cells play a significant role in the progress and maintenance of inflammatory processes in CUC.
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PMID:Mast cells and inflammatory mediators in chronic ulcerative colitis. 1208 39

Proteinase-activated receptor (PAR)-2, a G-protein-coupled receptor for trypsin and mast cell tryptase, is highly expressed in the intestine. Luminal trypsin and tryptase are elevated in the colon of inflammatory bowel disease patients. We hypothesized that luminal proteinases activate PAR-2 and induce colonic inflammation. Mice received intracolonically PAR-2 agonists (trypsin, tryptase, and a selective PAR-2-activating peptide) or control drugs (boiled enzymes, inactive peptide) and inflammatory parameters were followed at various times after this treatment. Colonic administration of PAR-2 agonists up-regulated PAR-2 expression and induced an inflammatory reaction characterized by granulocyte infiltration, increased wall thickness, tissue damage, and elevated T-helper cell type 1 cytokine. The inflammation was maximal between 4 and 6 hours and was resolved 48 hours after the intracolonic administration. PAR-2 activation also increased paracellular permeability of the colon and induced bacterial trans-location into peritoneal organs. These proinflammatory and pathophysiological changes observed in wild-type mice were not detected in PAR-2-deficient mice. Luminal proteinases activate PAR-2 in the mouse colon to induce inflammation and disrupt the integrity of the intestinal barrier. Because trypsin and tryptase are found at high levels in the colon lumen of patients with Crohn's disease or ulcerative colitis, our data may bear directly on the pathophysiology of human inflammatory bowel diseases.
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PMID:Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2. 1241 36

Historically, mast cells were known as a key cell type involved in type I hypersensitivity. Until last two decades, this cell type was recognized to be widely involved in a number of non-allergic diseases including inflammatory bowel disease (IBD). Markedly increased numbers of mast cells were observed in the mucosa of the ileum and colon of patients with IBD, which was accompanied by great changes of the content in mast cells such as dramatically increased expression of TNFalpha, IL-16 and substance P. The evidence of mast cell degranulation was found in the wall of intestine from patients with IBD with immunohistochemistry technique. The highly elevated histamine and tryptase levels were detected in mucosa of patients with IBD, strongly suggesting that mast cell degranulation is involved in the pathogenesis of IBD. However, little is known of the actions of histamine, tryptase, chymase and carboxypeptidase in IBD. Over the last decade, heparin has been used to treat IBD in clinical practice. The low molecular weight heparin (LMWH) was effective as adjuvant therapy, and the patients showed good clinical and laboratory response with no serious adverse effects. The roles of PGD2, LTC4, PAF and mast cell cytokines in IBD were also discussed. Recently, a series of experiments with dispersed colon mast cells suggested there should be at least two pathways in man for mast cells to amplify their own activation-degranulation signals in an autocrine or paracrine manner. The hypothesis is that mast cell secretogogues induce mast cell degranulation, release histamine, then stimulate the adjacent mast cells or positively feedback to further stimulate its host mast cells through H1 receptor. Whereas released tryptase acts similarly to histamine, but activates mast cells through its receptor PAR-2. The connections between current anti-IBD therapies or potential therapies for IBD with mast cells were discussed, implicating further that mast cell is a key cell type that is involved in the pathogenesis of IBD. In conclusion, while pathogenesis of IBD remains unclear, the key role of mast cells in this group of diseases demonstrated in the current review implicates strongly that IBD is a mast cell associated disease. Therefore, close attentions should be paid to the role of mast cells in IBD.
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PMID:Key role of mast cells and their major secretory products in inflammatory bowel disease. 1476 Jul 48

Bromelain is a complex mixture of proteinases typically derived from pineapple stem. Similar proteinases are also present in pineapple fruit. Beneficial therapeutic effects of bromelain have been suggested or proven in several human inflammatory diseases and animal models of inflammation, including arthritis and inflammatory bowel disease. However, it is not clear how each of the proteinases within bromelain contributes to its anti-inflammatory effects in vivo. Previous in vivo studies using bromelain have been limited by the lack of assays to control for potential differences in the composition and proteolytic activity of this naturally derived proteinase mixture. In this study, we present model substrate assays and assays for cleavage of bromelain-sensitive cell surface molecules can be used to assess the activity of constituent proteinases within bromelain without the need for biochemical separation of individual components. Commercially available chemical and nutraceutical preparations of bromelain contain predominately stem bromelain. In contrast, the proteinase activity of pineapple fruit reflects its composition of fruit bromelain>ananain approximately stem bromelain. Concentrated bromelain solutions (>50 mg/ml) are more resistant to spontaneous inactivation of their proteolytic activity than are dilute solutions, with the proteinase stability in the order of stem bromelain>fruit bromelain approximately ananain. The proteolytic activity of concentrated bromelain solutions remains relatively stable for at least 1 week at room temperature, with minimal inactivation by multiple freeze-thaw cycles or exposure to the digestive enzyme trypsin. The relative stability of concentrated versus dilute bromelain solutions to inactivation under physiologically relevant conditions suggests that delivery of bromelain as a concentrated bolus would be the preferred method to maximize its proteolytic activity in vivo.
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PMID:Proteinase activity and stability of natural bromelain preparations. 1571 Mar 46

The main objective of this study was to investigate the ability of histamine receptor antagonists to modulate tryptase release from human colon mast cells induced by histamine. Enzymatically dispersed cells from human colon were challenged with histamine in the absence or presence of the histamine receptor antagonists, and the tryptase release was determined. It was found that histamine induced tryptase release from colon mast cells was inhibited by up to approximately 61.5% and 24% by the H1 histamine receptor antagonist terfenadine and the H2 histamine receptor antagonist cimetidine, respectively, when histamine and its antagonists were added to cells at the same time. The H3 histamine receptor antagonist clobenpropit had no effect on histamine induced tryptase release from colon mast cells at all concentrations tested. Preincubation of terfenadine, cimetidine or clobenpropit with cells for 20 minutes before challenging with histamine did not enhance the ability of these antihistamines to inhibit histamine induced tryptase release. Apart from terfenadine at 100 microg/ml, the antagonists themselves did not stimulate tryptase release from colon mast cells following both 15 minutes and 35 minutes incubation periods. It was concluded that H1 and H2 histamine receptor antagonists were able to inhibit histamine induced tryptase release from colon mast cells. This not only added some new data to our hypothesis of self-amplification mechanisms of mast cell degranulation, but also suggested that combining these two types of antihistamine drugs could be useful for the treatment of inflammatory bowel disease (IBD).
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PMID:Inhibition of tryptase release from human colon mast cells by histamine receptor antagonists. 1599 73

Protease-activated receptor (PAR)-2 plays important roles in intestinal inflammatory responses. Changes in PAR-2-mediated smooth muscle function may contribute pathophysiologically to the intestinal motility disorders often observed in inflammatory bowel disease (IBD). Stimulation of PAR-2 by trypsin-induced relaxation of carbachol- and KCl-induced contractions in normal rat colonic smooth muscle was completely resolved by tissue pretreatment with apamin, but not by pretreatment with l-NMMA or a cocktail of neuronal blockers (tetrodotoxin, hexamethonium and propranolol). In colon inflamed by dextran sodium sulphate (DSS), trypsin-induced inhibitory effects were significantly reduced. Relaxation induced by SLIGRL-NH(2), a selective PAR-2-activating peptide, was also reduced in DSS-treated rat colon. However, inhibitory effects of 1-ethylbenzimidazolin-2-one, an activator of small conductance Ca(2+)-activated K(+) channel, were unaffected. Expression of PAR-2 mRNA in colonic muscularis externa was significantly lower in DSS-treated rats than in control rats. These results suggest that the PAR-2 mediated relaxation system in colonic smooth muscle is suppressed in this experimental colitis rat model, and may contribute to motility disorders in IBD.
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PMID:Impairment of PAR-2-mediated relaxation system in colonic smooth muscle after intestinal inflammation. 1652 Jul 39

Intestinal epithelial cells (IEC) are constantly exposed to both high concentrations of the bacterial ligand LPS and the serine protease trypsin. MD-2, which contains multiple trypsin cleavage sites, is an essential accessory glycoprotein required for LPS recognition and signaling through TLR4. The aim of this study was to characterize the expression and subcellular distribution of intestinal epithelial MD-2 and to delineate potential functional interactions with trypsin and then alteration in inflammatory bowel disease (IBD). Although MD-2 protein expression was minimal in primary IEC of normal colonic or ileal mucosa, expression was significantly increased in IEC from patients with active IBD colitis, but not in ileal areas from patients with severe Crohn's disease. Endogenous MD-2 was predominantly retained in the calnexin-calreticulin cycle of the endoplasmic reticulum; only a small fraction was exported to the Golgi. MD-2 expression correlated inversely with trypsin activity. Biochemical evidence and in vitro experiments demonstrated that trypsin exposure resulted in extensive proteolysis of endogenous and soluble MD-2 protein, but not of TLR4 in IEC, and was associated with desensitization of IEC to LPS. In conclusion, the present study suggests that endoplasmic reticulum-associated MD-2 expression in IBD may be altered by ileal protease in inflammation, leading to impaired LPS recognition and hyporesponsiveness through MD-2 proteolysis in IEC, thus implying a physiologic mechanism that helps maintain LPS tolerance in the intestine.
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PMID:Trypsin-sensitive modulation of intestinal epithelial MD-2 as mechanism of lipopolysaccharide tolerance. 1654 63

Mast cells were described by Erhlich at the end of XIX-th century. Their role was deeply investigated in asthma and allergy. The massive degranulation of mast cells in allergy can lead to anaphylactic shock. Recently, mast cells have been recognized again as a very interesting topic for investigation, due to their possible role in chronic inflammation. Moreover, through adenosine receptors, mast cells can be activated or inactivated. That is why these cells are regarded as a potential target of new drugs. It has been reported, that mast cells generate intracellular reactive oxygen species (ROS) in response to stimulation with divergent physiologically relevant stimulants. The intensification of ROS production may be measured by the level of carbonyl groups, as a marker of protein peroxidation. However, the role of mast cells in other than asthma diseases with chronic inflammation needs further investigation. It was found out that the information about mast cell distribution in colonic mucosa may serve as help in differentiation between inflammatory bowel disease and collagenous colitis. Moreover, its accumulation in focal active gastritis was confirmed in patients with Crohn's disease. An important role in regulation of inflammatory process seems to be reserved for adenosine receptors present on mastocytes. The activation of mast cells through the adenosine receptor is connected with 11-8 release, which stimulate the migration of leukocytes and oxidation reactions. The detection of mast cells in tissues should not be limited only to the simple histologic examination. It should be completed by the detection of products of degranulation, e.g. tryptase. This is the way to find out their actual function and state of activation.
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PMID:[Mast cells, their adenosine receptors and reactive oxygen species in chronic inflammatory pathologies of childhood]. 1720 8

It has been suggested but not proven that hypersensitivity type I reactions are involved in the pathogenesis of canine inflammatory bowel disease (IBD). The main effector cells in type I hypersensitivity reactions are mast cells (MCs). Canine MCs, as human MCs, can be subdivided into three subtypes according to their content of mast cell-specific proteases: tryptase (MCT), chymase (MCC), or tryptase and chymase bearing MCs (MCTC). In this study, numbers and subsets of mast cells were investigated in biopsies from the gastrointestinal tract of dogs with histopathologically confirmed lymphocytic-plasmacytic enteritis (LPE) (n=4), lymphocytic-plasmacytic colitis (LPC) (n=1) and eosinophilic gastroenterocolitis (EGE) (n=11). Paraffin sections of formalin-fixed samples from the stomach, small intestine (duodenum, jejunum, ileum) and colon were stained by using a metachromatic staining method (kresylecht-violet; KEV) and a combined enzyme histochemical and immunohistochemical technique for chymase and tryptase. Additionally, immunohistochemistry with antibodies against T cells (CD3), macrophages (myeloid/histiocyte antigen) and IgA, IgG and IgM bearing cells was conducted. Quantitative evaluation of mast cells and semiquantitative scoring of immunohistochemically stained cells were performed. Between the two histopathologically defined groups clear differences concerning mast cell numbers were detected. In most affected intestinal tissue locations of dogs with LPE/LPC a decrease in metachromatically (kresylecht-violet) stained granule-containing MCs and immunohistochemically stained MCT,C,TC was found. This reduction could be due to mast cell degranulation, a T helper cell 1 dominated reaction pattern or a "thinning out" due to increasing T cells, IgA and IgG bearing cells. Dogs with EGE displayed higher variability in mast cell numbers but most of the affected large and small intestinal locations had increased numbers of MCs. In these cases, T cells, IgA bearing cells and macrophages also increased. Increased numbers of MCs and eosinophils seen in the intestinal mucosa of dogs with EGE could indicate the presence of a type I hypersensitivity reaction (T helper cell 2 pattern) in response to dietary antigens. Changes in cell numbers occurred also in unaffected locations of dogs with LPE/LPC and EGE which showed reduced MCT,C,TC, increased KEV positive cells and partially increased leucocytes and macrophages.
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PMID:Characterization of mast cell numbers and subtypes in biopsies from the gastrointestinal tract of dogs with lymphocytic-plasmacytic or eosinophilic gastroenterocolitis. 1785 Aug 82

The potential role of the mast cells in the invasion of very virulent infectious bursal disease virus (vvIBDV) is unknown. We evaluated mast cell activity and tryptase production after vvIBDV infection in special pathogen-free (SPF) chickens using cytochemistry and immunohistochemistry analyses. The results were as follows: (1) severe histologic lesions were observed in the thymus, spleen, cloacal bursa, liver, kidney and other tissues. vvIBDV viral antigens were detected and presented extensively in the parenchymatous organs, in particular, the cloacal bursa, liver, kidney, thymus, spleen and pancreas. (2) In the vvIBDV-infected group, the mast cell population increased markedly in the liver, kidney, thymus, glandular stomach, spleen and cloacal bursa on days 1, 2 and 3 after vvIBDV infection (p<0.05). However, very few mast cells were observed in those same tissues in the controls, especially in the bursa of Fabricius. (3) Tryptase, a marker for activated mast cells, has a positive correlation with mast cell distribution. The mast cells identified in the tissues were likely to be activated since they were associated with cell degranulation and the presence of tryptase. Furthermore, the co-localization of mast cells, and presence of vvIBDV antigens suggests that the mast cells were activated by vvIBDV infection. Our results also suggest that tryptase may contribute to the inflammation of acute IBD induced by vvIBDV infection. Our research contributes to the further understanding of inflammatory response mechanisms and the contribution of mast cell activity to this process.
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PMID:Mast cell mediated inflammatory response in chickens after infection with very virulent infectious bursal disease virus. 1834 56


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