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)

Interleukin 13 (IL-13), a member of the a-helical family of cytokines, has approximately 30% primary sequence homology with IL-4 and shares a common receptor component. The biologically active rhIL-13 is monomeric and non-glycosylated, and contains two disulfide bonds as determined by comparative electrospray mass spectrometric (MS) analysis of the protein before and after reduction with dithiothreitol-dithioerythritol. A trypsin-resistant core peptide of rhIL-13 was isolated and analyzed by plasma desorption (PD) MS, identifying a disulfide-linked core peptide. Subsequent digestion of this core peptide by pepsin, followed by PDMS analysis of the resulting cystine-containing peptic fragments, provided rapid determination of the existing disulfide bonds between cysteine residues 28-56 and 44-70. This disulfide arrangement is similar to that observed for the analogous four internal cysteine residues in hIL-4. The conservation of disulfide bond arrangements between hIL-13 and hIL-4, coupled with their alpha-helical structure and sequence homologies, confirms that IL-13 and IL-4 are structural homologues. It is also consistent with their reported similarities in biological function and receptor binding kinetics.
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PMID:Mass spectrometric mapping of disulfide bonds in recombinant human interleukin-13. 1076 76

Tryptase and myeloperoxidase respectively represent 2 specific markers of activated mast cells or neutrophils. Therefore, establishing the levels of these enzymes may be useful to quantify the cell involvement in the tissues or fluids of different origins and in different pathologies. The aim of this study was to analyse the levels of these 2 markers in both the sera and blister fluids of patients affected with bullous pemphigoid. These levels were then correlated to the concentrations of 19 cytokines and 2 soluble adhesion molecules determined in the same samples and also with the log (anti-basement membrane zone antibody) titres, evaluated in the patients' sera. For these purposes, 15 patients with bullous pemphigoid (10 males and 5 females; median age: 84 years, range 66-87; median disease duration: 0 years, range 0-3: median number of skin lesions: 17, range 14-30; median anti-basement membrane zone antibody titre: 1:320, range 0.0-1:2560) and 15 normal subjects (11 males and 4 females, median age: 81 years, range 59-86) were analysed by means of commercially available kits. Results showed that blister fluid myeloperoxidase and tryptase levels were increased as compared with the respective sera (P<0.01) and several correlations were observed with cytokines and adhesion molecules. In fact, significant correlations of blister fluid tryptase levels were observed with IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, VEGF, RANTES and sICAM-1, while myeloperoxidase was correlated with IL-1beta, IL-13 and IL-15. The blister fluid tryptase levels were also significantly correlated with the anti-basement membrane zone antibody titres (R=0.53, P=0.05). In conclusion, these findings are in accord with an involvement of both mast cells and neutrophils in bullous pemphigoid and their recruitment may be mediated by different biological modulators. Our findings seem to indicate that the cytokine (IL-3, IFN-gamma and OSM) or adhesion molecule (sICAM-1) concentrations in blister fluid are logarithmically related to the anti-basement membrane zone antibody titers.
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PMID:Increased tryptase and myeloperoxidase levels in blister fluids of patients with bullous pemphigoid: correlations with cytokines, adhesion molecules and anti-basement membrane zone antibodies. 1077 87

Mast cells can be found in contact with epidermis in certain circumstances; especially in chronic inflammatory skin diseases and chronic ulcers, but the significance of this association is obscure. In this study, the association of mast cells with wound healing was studied by counting mast cells in the wound edges at different stages after wounding the donor site skin for pinch-grafting. Chronic venous leg ulcers were biopsed for comparison. Tryptase- and chymase-positive mast cells were stained enzyme-histochemically for active proteinases. Both the number of tryptase-positive, i.e. total mast cells, and chymase-positive mast cells decreased during wound healing, but only the change in chymase-positive mast cells was statistically significant (P< or =0.03) the maximal decrease being 63% on day 7. No mast cells could be found in the vicinity of epithelialization margin. In venous leg ulcers, significantly more mast cells were present in the perilesional skin near the epithelium margin than in the wound bed (P=0.03), and mast cells were also seen in close contact with the basement membrane. Immunoreactivity for IL-4 and TNF-alpha in mast cells was studied to see if either of these molecules was associated with wound healing. In normally healing wounds, only a minority of mast cells were immunoreactive for these cytokines and no change in positive mast cell numbers could be seen during wound healing. In chronic wounds, IL-4 was absent in mast cells, and TNF-alpha positive mast cells were present only in perilesional skin and in small numbers. These results show that mast cells especially chymase-positive - decrease in number and can not be found in the epithelialization zone in normal wound healing, whereas tryptase-positive mast cells are associated with delayed wound healing and epithelialization in chronic wounds. Thus it seems, that mast cells attempt to control hyperproliferation of epidermis in chronic wounds.
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PMID:Alterations in mast cells showing tryptase and chymase activity in epithelializating and chronic wounds. 1094 47

Changes in the levels of cytokines in the circulating blood and skin have been reported in patients with atopic dermatitis (AD). We determined IFN-gamma, IL-2, IL-4, IL-5 and IL-10 in both the serum and plasma of 45 AD patients and 20 healthy donors. Since differences in the levels of these cytokines between serum and plasma were found, the roles of Ca2+ and proteolytic enzymes were examined. Levels of IL-2 and IL-10 were measured in citrated plasma to which various amounts of CaCl2, protease inhibitors, and proteases had been added. All cytokine determinations were carried out using a standard ELISA. The plasma levels of IFN-gamma, IL-2, and IL-5 were significantly elevated, but the serum levels of these cytokines were not significantly changed. The levels of IL-2 in the plasma of the AD patients averaged 4.25-fold higher than in the serum of the AD patients, and 2.5-fold higher than in the plasma of healthy controls (P < 0.001). CaCl2 produced a dose-dependent decrease in IL-2 and IL-10 in citrated plasma. The protease inhibitors PMSF, aprotinin and leupeptin produced a dose-dependent increase in measurable levels of IL-2 and IL-10 in plasma. A decrease in IL-2 levels was also seen in CaCl2-supplemented serum-free medium, and this was accentuated by the addition of the proteases thrombin, trypsin, chymotrypsin and elastase. These findings suggest that although significant changes in cytokine levels have been reported not to occur in circulating blood but have been reported to occur in the skin of AD patients both in vivo and in vitro, cytokines can indeed also be found to be elevated in circulating blood when assessed carefully by statistically valid methods. Further, it is suggested that during the preparation of serum, some circulating cytokines are degraded by calcium-dependent proteases, and that Ca2+ itself can also affect the measurement of cytokines. The measurement of circulating cytokines needs to be carefully reassessed.
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PMID:Evidence for degradation of cytokines in the serum of patients with atopic dermatitis by calcium-dependent protease. 1099 73

The immunological response of infants younger than six months to infection with respiratory syncytial virus (RSV) was studied in relation to clinical severity. IL-6 and IL-8 were found more frequently and at higher levels in the plasma samples of more severely ill patients and no significant differences were found in the levels of cytokines differentiating between Type 1 and Type 2 responses. Cellular infiltrates in nasopharyngeal washings consisted mainly of polymorphonuclear granulocytes and monocytes. Eosinophils, IgE positive cells and tryptase positive cells were found sporadically. Analyses of RSV stimulated T cell cultures established from peripheral blood mononuclear cells, for intracellular and secreted cytokines showed that, irrespective of clinical severity, the responses were dominated by the production of IFN-gamma, and that only low levels of IL-4 and IL-10 were detectable. Collectively these data do not indicate an association between clinical severity and a Type 2-like T cell response.
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PMID:Type 1-like immune response is found in children with respiratory syncytial virus infection regardless of clinical severity. 1100 58

IL-4, IL-5, tryptase and eosinophil cationic protein levels were measured in nasal lavage fluid from 15 pollen allergic rhinitis beyond pollen season. Allergy was proved by prick test. There were 15 non allergic children in the control group. Specific nasal allergen provocation was performed on the rhinitic group. Nasal lavage were done before, 1 and 12 hours after the provocation. Before the nasal provocation the ECP and IL-4 levels were significantly higher in the allergic group compared to the non allergic group. The levels of tryptase, ECP and IL-4 rose significantly after the provocation. The results reflect to the possibility of an activated immune status in allergic rhinitis even without the presence of the triggering pollens. After the specific provocation elevated tryptase levels were measured, referring to the activity of the early phase of the I. type hypersensitivity reaction, while the ECP and IL-5 elevation to its late phase. According to our examinations it can be said, that tryptase, ECP and IL-5 might be used to detect the activation of the early and late phases of the IgE mediated hypersensitive reaction.
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PMID:[Levels of interleukin-4, interleukin-5, tryptase and eosinophil cationic protein of nasal lavage fluid in pollen allergic rhinitis]. 1101 93

Pemphigus vulgaris and pemphigus foliaceus are commonly known as antibody-mediated bullous diseases. However, recently a role for infiltrating cells as contributors to the pathogenesis of these diseases has been suggested. The aims of our study were to characterize the immunophenotype of the cellular infiltrate of pemphigus lesional skin and to study the cytokines secreted. We have therefore performed an immunohistochemical study with a large panel of monoclonal antibodies (to CD3, CD4, CD8, CD25, CD30, myeloperoxidase, eosinophil cationic protein EG2, tryptase, human interleukin (IL)-2, human IL-4, human IL-5, human IL-6, human IL-8, and interferon (IFN)-gamma using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and uninvolved skin of six patients with clinical, histological, and immunofluorescent proven pemphigus. We also performed RT-PCR in order to demonstrate mRNA expression of the cytokines of interest. Our results suggest the presence of a T cell population with a prevalent Th2-like cytokine pattern in lesional skin. In addition, we demonstrate a consistent number of granulocytes and mast cells that show clear signs of activation. These data suggest the involvement of an inflammatory infiltrate in the production of pemphigus lesions. In particular, we assume that Th2 cells may be implicated in the very early stages of autoimmune response, concluding that they exert broad activity in blister formation.
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PMID:Further support for a role for Th2-like cytokines in blister formation of pemphigus. 1116 84

In airways, mast cells lie adjacent to nerves, blood vessels and lymphatics, which highlights their pivotal importance in regulating allergic inflammatory processes. In asthma, mast cells are predominantly activated by IgE receptor cross linking. In response to activation, preformed mediators that are stored bound to proteoglycans, for example, TNF-alpha, IL-4, IL-13, histamine, tryptase and chymase, are released. New synthesis of arachidonic acid metabolites (leukotriene C4 (LTC4), leukotriene B4 (LTB4) and prostaglandin D2 (PGD2)) and further cytokines is stimulated. Mediators from degranulating mast cells are critical to the pathology of the asthmatic lung. Mast cell proteases stimulate tissue remodelling, neuropeptide inactivation and enhanced mucus secretion. Histamine stimulates smooth muscle cell contraction, vasodilatation and increased venular permeability and further mucus secretion. Histamine induces IL-16 production by CD8+ cells and airway epithelial cells; IL-16 is an important early chemotactic factor for CD4+ lymphocytes. LTC4, LTB4 and PGD2 affect venular permeability and can regulate the activation of immune cells. The best characterized mast cell cytokine in asthmatic inflammation is TNF-alpha, which induces adhesion molecules on endothelial cells and subsequent transmigration of inflammatory leucocytes. IL-13 is critical to development of allergic asthma, although its mode of action is less clear.
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PMID:Regulation of the inflammatory response in asthma by mast cell products. 1126 9

Mature human mast cells are tissue-residing, key effector cells of immediate allergic reactions. Moreover, mast cells have been recognized as a potent cellular source of multiple cytokines, suggesting an important role in immunoregulation and host defense. Here, we report on the regulation of mature human mast cells isolated from intestinal tissues by stem cell factor (SCF) and interleukin (IL)-4. SCF is substantially necessary for mast cell survival and induces marginal mast cell proliferation in vitro, whereas IL-4 by itself has no effects on mast cell survival or proliferation. Most interestingly, in synergy with SCF, IL-4 strongly enhances mast cell proliferation. In the presence of SCF, mast cells predominantly produce pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6, IL-8, IL-16, and IL-18. Addition of IL-4 to the culture medium induces the expression of Th2-type cytokines (IL-3, IL-5 and IL-13), and a downregulation of pro-inflammatory cytokines, namely IL-6. Furthermore, SCF by itself supports the predominance of the tryptase/chymase double-positive mast cell subtype MCTC whereas the addition of IL-4 supports the chymase negative MCT subtype. In conclusion, SCF may primarily regulate resident mast cell survival, whereas IL-4 may promote local proliferation of mast cells and their expression of Th2-type cytokines.
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PMID:Regulation of human intestinal mast cells by stem cell factor and IL-4. 1129 28

Desloratadine is a new, selective, H(1)-receptor antagonist that also has anti-inflammatory activity. In vitro studies have shown that desloratadine inhibits the release or generation of multiple inflammatory mediators, including IL-4, IL-6, IL-8, IL-13, PGD(2), leukotriene C(4), tryptase, histamine, and the TNF-alpha-induced chemokine RANTES. Desloratadine also inhibits the induction of cell adhesion molecules, plateletactivating factor-induced eosinophil chemotaxis, TNF-alpha-induced eosinophil adhesion, and spontaneous and phorbol myristate acetate-induced superoxide generation in vitro. In animals desloratadine had no effect on the central nervous, cardiovascular, renal, or gastrointestinal systems. Desloratadine is rapidly absorbed, has dose-proportional pharmacokinetics, and has a half-life of 27 hours. The absorption of desloratadine is not affected by food, and the metabolism and elimination are not significantly affected by the subject's age, race, or sex. There are no clinically relevant interactions between desloratadine and erythromycin, ketoconazole, or grapefruit juice. Desloratadine is not a significant substrate of the P-glycoprotein transport system. Once daily administration of desloratadine rapidly reduces the nasal and nonnasal symptoms of seasonal allergic rhinitis, including congestion. In patients with seasonal allergic rhinitis and concomitant asthma, desloratadine treatment was also associated with significant reductions in total asthma symptom score and use of inhaled beta(2)-agonists. Use of desloratadine in patients with chronic idiopathic urticaria was associated with significant reductions in pruritus, number of hives, size of the largest hive, and interference with sleep and daily activities. Clinical experience in over 2300 patients has shown that the adverse event profile of desloratadine is similar to that of placebo; desloratadine has no clinically relevant effects on electrocardiographic parameters, does not impair wakefulness or psychomotor performance, and does not exacerbate the psychomotor impairment associated with alcohol use.
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PMID:Desloratadine: A new, nonsedating, oral antihistamine. 1129 78


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