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)

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

The microenvironment of secondary lymphoid organs consists of two major populations of cells, the lymphoid cells and a population of stromal cells that contribute to both tissue architecture and function. Interactions of both populations are essential for the development and control of humoral immune responses. In this study, stromal-cell preparations were obtained by a multistage process. This involved culturing 300-400-microm slices of human tonsil for 6-8 days at 25 degrees C, trypsin digestion of the residual explant, followed by CD45-positive-cell depletion using magnetic beads, and a final period of culture for 4 days to remove remaining nonadherent cells. Phenotyping with a panel of monoclonal antibodies revealed that the cells express HLA-DR, CD54 (ICAM-1), CD44, but no CD45 nor a range of other markers for epithelial and endothelial cells. Immunoassays of supernatants from stromal cells revealed that IL-6 was produced constitutively, and its production was increased by treatment with TNF-alpha and IFN-gamma. In contrast IL-1, IL-2, IL-4, IL-7, IL-8, IL-10, IL-12, TNF-alpha, and IFNgamma were not produced. Functional tests showed that these cells express follicular dendritic cell-like properties. Coculturing of tonsilar B cells with stromal cells resulted in enhanced proliferation and also led to increased production of immunoglobulins and IL-6, suggesting crucial signaling between these populations.
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PMID:Tonsil stromal-cell lines expressing FDC-like properties: isolation, characterization, and interaction with B lymphocytes. 981 1

When we assessed cytokine levels in both plasma and serum from the patients with atopic dermatitis and healthy volunteers, we found that IL-2, 5 and 10, and IFN-gamma were significantly elevated in the plasma from atopic dermatitis patients but not in their sera and that, in an average, each cytokine level, especially IL-2 level is far higher in plasma than in serum. In order to solve the cause for this dissociation. Calcium ion was dose-dependently added in the plasma in which calcium ion had been inactivated by citrate contained in the plasma. Protease inhibitors, PMSF, aprotinin and leupeptin were added in the plasma in which each cytokine was decreased in the presence of calcium ion. Finally, in RPMI medium where cytokine IL-2 or IL-10 is present, proteases, thrombin, trypsin and chymotrypsin themselves were introduced. Results revealed that addition of calcium ion dose-dependently decreased each cytokine level in the plasma, respectively. Protease inhibitors, PMSF, aprotinin and leupeptin significantly elevated each cytokine level in the plasma where cytokines had been decreased by the presence of calcium ion, respectively. These changes were comparable between plasma and blood cell-containing plasma, attesting that the effect of enzymes released from the calcium ion-activated neutrophil granules on the decrease in cytokine levels is negligible. Cytokines, IL-2 itself was also decreased in the presence of calcium ion alone, or in the presence of both proteases, thrombin, trypsin or chymotrypsin itself, and calcium, respectively. This study suggests that calcium ion itself or calcium ion-activated protease may denature the cytokine and that for this reason, cytokine should be, in general in our laboratory, assessed in not serum but plasma.
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PMID:[Cytokine assessed in the serum are denatured by calcium ion and resultantly activated protease]. 1022 85

Recently, it has emerged that extracellular proteases have specific regulatory roles in modulating immune responses. Proteases may act as signaling molecules to activate the Raf-1/extracellular regulated kinase (ERK)-2 pathway to participate in mitogenesis, apoptosis, and cytokine production. Most reports on the role of protease-mediated cell signaling, however, focus on their stimulatory effects. In this study, we show for the first time that extracellular proteases may also block signal transduction. We show that bromelain, a mixture of cysteine proteases from pineapple stems, blocks activation of ERK-2 in Th0 cells stimulated via the TCR with anti-CD3epsilon mAb, or stimulated with combined PMA and calcium ionophore. The inhibitory activity of bromelain was dependent on its proteolytic activity, as ERK-2 inhibition was abrogated by E-64, a selective cysteine protease inhibitor. However, inhibitory effects were not caused by nonspecific proteolysis, as the protease trypsin had no effect on ERK activation. Bromelain also inhibited PMA-induced IL-2, IFN-gamma, and IL-4 mRNA accumulation, but had no effect on TCR-induced cytokine mRNA production. This data suggests a critical requirement for ERK-2 in PMA-induced cytokine production, but not TCR-induced cytokine production. Bromelain did not act on ERK-2 directly, as it also inhibited p21ras activation, an effector molecule upstream from ERK-2 in the Raf-1/MEK/ERK-2 kinase signaling cascade. The results indicate that bromelain is a novel inhibitor of T cell signal transduction and suggests a novel role for extracellular proteases as inhibitors of intracellular signal transduction pathways.
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PMID:Bromelain, from pineapple stems, proteolytically blocks activation of extracellular regulated kinase-2 in T cells. 1045 95

In an attempt to generate murine natural killer (NK) cell-specific monoclonal antibodies (MAbs) by immunizing Balb/c mice with C57BL/6 (B6) A-LAKs, we have isolated a hybridoma, CS/NicT.2, which secretes an IgM that recognizes a majority of B6 and B6 Rag-1-/- A-LAKs. The CS/NicT.2 antigen is highly expressed by A-LAKs, but only at extremely low levels on resting splenocytes, suggesting that its expression is tightly associated with IL-2 activation. Among the cell lines examined, only CTLL-2 expresses the CS/NicT.2 antigen at relatively high levels. A low level of CS/NicT.2 staining is also detected on resting allo-specific cytotoxic T lymphocytes (CTL) clones, AB.1 and C11. In addition, a similar low level of CS/NicT.2 staining is detected on the T-helper cell line HT-2. The CS/NicT.2 antigen is upregulated by ionomycin but not by phorbol 12-myristate 13-acetate (PMA). For the CTL clones examined, CS/NicT.2 staining is also dramatically increased by anti-TCRbeta or anti-CD3epsilon stimulation. Protease treatments of CTLL-2 show that this antigen is proteinase K sensitive, but relatively resistant to trypsin digestion. Furthermore, the CS/NicT.2 antigen exhibits a relatively fast turnover rate as assessed by proteinase K and cycloheximide treatments of CTLL-2, suggesting that the CS/NicT.2 antigen may have a short half-life on the cell surface.
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PMID:Generation and characterization of a monoclonal antibody that recognizes an activation antigen expressed by a majority of adherent lymphokine-activated killer cells. 1076 41

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

A potent inhibitor of mitogen-stimulated T cell proliferation exists in the saliva of several species of hard ticks, including the Lyme disease vector tick, Ixodes scapularis. Our characterization of this phenomenon has led to the identification of a possible mechanism for the T cell inhibitory activity of I. scapularis saliva. The T cell inhibitor can overcome stimulation of mouse spleen cells with anti-CD3 mAb; however, a direct and avid interaction with T cells does not appear to be necessary. Tick saliva inhibits a mouse IL-2 capture ELISA, suggesting that a soluble IL-2 binding factor is present in the saliva. This hypothesis was verified by using a direct binding assay in which plate-immobilized tick saliva was shown to bind both mouse and human IL-2. Elimination of the IL-2 binding capacity of saliva in the in vitro assays by trypsin digestion demonstrated that the IL-2 binding factor is a protein. These experiments comprise the first demonstration of the existence of such a secreted IL-2 binding protein from any parasite or pathogen. This arthropod salivary IL-2 binding capacity provides a simple mechanism for the suppression of T cell proliferation as well as for the activity of other immune effector cells that are responsive to IL-2 stimulation. Relevance of the tick T cell inhibitory activity to the human immune system is demonstrated by the ability of tick saliva to inhibit proliferation of human T cells and CTLL-2 cells grown in the presence of human IL-2.
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PMID:Identification of an IL-2 binding protein in the saliva of the Lyme disease vector tick, Ixodes scapularis. 1125 84

Symptoms of nasal, pharyngeal and ocular discomfort have been reported among workers in the wood surface-coating industry. Symptoms were reported more often by workers using ultraviolet radiation-curable acrylate coatings (UV coatings), which contain potential chemical sensitizers, than by those using acid-curing coatings. Furthermore, increased levels of eosinophil cationic protein (ECP) and albumin, but not tryptase, in nasal lavage from workers exposed to UV coatings have been observed. To further examine whether air contaminants present in the UV-coating industry are causing the observed increase in symptoms, the inflammatory process in the nasal mucosa of workers exposed to UV coatings was investigated. Clinical and biochemical endpoints were selected to distinguish between specific and non-specific hypersensitivity and to test the hypothesis that the symptoms were consistent with Type IV hypersensitivity. The nasal lavage and nasal biopsy were performed under local anesthetic at the workplace during working hours after a minimum of 2 h of work in both the exposed and control groups. Albumin and ECP, and the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8), were used as inflammatory markers. A multi-probe ribonuclease protection assay was used to attempt to detect cytokine variation in human nasal biopsies. The cytokine genes analyzed were TNF-alpha, GM-CSF, interferon-gamma, IL-2, IL-4 and IL-5. L32 and GAPDH were used as control genes for mRNA expression levels. Mucosal inflammation symptoms correlated with increased levels of albumin, but not with increased levels of ECP, secreted proinflammatory cytokines or cytokine gene mRNA expression. We conclude that the symptoms are non-specific and do not correlate with occupational exposure to UV coatings under the conditions of this investigation.
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PMID:Absence of proinflammatory cytokine gene expression in nasal biopsies from wood surface-coating industry workers. 1167 74

The objectives of this study were to assess the modulation of T-cell CD3-zeta expression by factor(s) present in sera of pregnant women, to correlate this activity with markers of T-cell function associated with pregnancy, and to identify the presence of a circulating pregnancy-associated factor responsible for the suppression of CD3-zeta chain. The suppression of TcR/CD3-zeta expression on cultured T-lymphocytes (Jurkat cells) by sera and amniotic fluids from pregnant women was examined by Western immunoblots and quantitated by densitometry. This suppression was correlated with the induction of T-cell apoptosis and reduced production of IL-2. The serum component suppressing zeta expression was characterized by ultrafiltration and protease sensitivity. Incubation of Jurkat cells with sera obtained from women in the first trimester produced a slight, but not statistically significant, suppression of zeta expression; however, sera from pregnant women in the second and third trimesters and amniotic fluids significantly suppressed zeta levels in a dose-dependent manner. The loss of zeta chain correlated with both reduced secretion of IL-2 and induction of lymphocyte apoptosis. Fractionation of sera by ultrafiltration demonstrated that the zeta chain suppressive factor was <5 kDa, and its trypsin-sensitivity suggests a proteinaceous moiety. Pregnancy is associated with a progressive suppression of cell-mediated immunity. These suppressed T-cell functions have been linked to Fas/Fas ligand-induced apoptosis and suppression of Th1 cytokines, including IL-2. We demonstrate that these pregnancy-associated events are mimicked by a factor(s) present in patient-derived fluids. Suppression of zeta expression appears to be due to a circulating low-molecular-weight protein that suppresses CD3-zeta in a concentration-dependent manner.
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PMID:Modulation of T-cell CD3-zeta chain expression during normal pregnancy. 1183 93

Interleukin (IL)-16 is a homotetramer of 14-kDa subunits discovered in 1982 as a T-cell-specific chemoattractant factor. IL-16 plays a role in trafficking of several immune cells and may be a major chemotactic signal for CD4+ cells. Here, we review some of the key biological actions of IL-16. Because this cytokine has been shown to affect the levels of many inflammatory mediators such as histamine, serotonin, regulated upon activation, normal T cell expressed and secreted (RANTES), and monocyte chemotactic protein-1 (MCP-1), and other cytokines such as IL-2, we investigated the effect of IL-16 on control and stimulated human umbilical cord blood-derived cultured mast cells after antigen challenge. We found that human recombinant IL-16 (0.2-200 ng/mL) does not affect either basal tryptase or IL-8 release or that induced by anti-immunoglobulin E activation. In accordance with other data in the medical literature, we conclude that the most important function of IL-16 is the chemoattraction of CD4+ cells.
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PMID:Interleukin-16 network in inflammation and allergy. 1200 88


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