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)

This study investigates the possible involvement of serine proteases in interferon-gamma (IFN-gamma) activity on WISH cells. It was observed that inhibition of (3)H-thymidine incorporation induced by IFN-gamma was abrogated by the serine protease inhibitors Nalpha-tosyl-L-lysyl-chloromethane and soybean trypsin inhibitor, both of which act mainly on trypsin. Phenylmethyl sulfonyl fluoride also had a partial inhibitory effect. Other protease inhibitors specific to the cysteine, the aspartic, and the metalloprotease families were not effective. Kinetic analysis revealed that a trypsin-like protease is involved in IFN-gamma activity for up to 7 h. Trypsin-like activity induced by IFN-gamma was detected in the particulate fraction but not in the cytosolic fraction, whereas chymotrypsin activity was not enhanced in either the cytosolic or particulate fractions under similar conditions. Following separation on a gelatin substrate gel, two trypsin-like protease activities located in the particulate fraction were found to increase in response to IFN-gamma treatment. Hence, it seems that a specific membrane-associated trypsin-like protease activity induced by IFN-gamma may play a role in the action of the cytokine on thymidine incorporation in WISH cells.
J Interferon Cytokine Res 2002 Aug
PMID:Involvement of proteases in the action of IFN-gamma on WISH cells. 1239 23

Presence of mast cells and an increase in the concentration of their products has been reported in multiple sclerosis (MS) plaques. The most abundant secretory mediator of the human mast cell is the tetrameric protease tryptase. We demonstrate that tryptase can activate peripheral mononuclear cells (PBMCs), isolated from healthy donors as well as MS patients for the release of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-1beta. Cytokine secretion was significantly higher in secondary progressive (SP) MS patients and healthy control (HC) individuals than in relapsing-remitting (RR) patients. Our findings suggest that tryptase is, most probably, an important mediator of inflammation in MS.
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PMID:Tryptase activates peripheral blood mononuclear cells causing the synthesis and release of TNF-alpha, IL-6 and IL-1 beta: possible relevance to multiple sclerosis. 1274 61

2'-5'-Oligoadenylate synthetase (OAS), an interferon (IFN) induced enzyme, synthesizes 2'-5'-oligoadenylate (2-5A) from ATP when activated by dsRNA. Chicken OAS (ChOAS) has a ubiquitin-like (UbL) domain of two consecutive sequences (UbL1 and UbL2) at its carboxyl-terminus. The OAS gene has at least two alleles, OAS*A and OAS*B. OAS-A is the wild-type (wt) and OAS-B is a mutant deleted of a highly hydrophobic region of UbL1. To study the function of the UbL domain, enzymatic and physiologic properties were compared between OAS-A and OAS-B. OAS-B was more susceptible to trypsin than OAS-A and was converted very quickly into p38, deleting a greater part of the UbL domain. The p38 has the enzymatic activity to synthesize 2-5A. Thermal inactivation of OAS-B occurred at a lower temperature than that of OAS-A and p38, with loss of the ability to bind dsRNA. In contrast to OAS-A, the content of OAS-B in erythrocytes decreased during growth to a very low level. However, red blood cells (RBC) from anemic B/B chickens synthesized OAS-B at a high level comparable to A/A, although OAS-B levels decreased sharply again during maturation to erythrocytes. Thus, OAS-B carrying the mutated UbL domain is unstable compared with OAS-A in vitro and in vivo, and the wt UbL domain may contribute to the stability of the protein structure of ChOAS.
J Interferon Cytokine Res 2003 Nov
PMID:Function of ubiquitin-like domain of chicken 2'-5'-oligoadenylate synthetase in conformational stability. 1465 81

In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/ or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-gamma), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22-57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-gamma showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system.
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PMID:Infiltrating cells and related cytokines in lesional skin of patients with chronic idiopathic urticaria and positive autologous serum skin test. 1470 3

Colony-stimulating factors (CSFs)-induced increased hematopoietic activity is known to occur in various microbial diseases; however, not much is known during tuberculosis (TB). We investigated the CSF-inducing capability of a Mycobacterium tuberculosis H37Rv component. Swiss mice intravenously injected with purified 30-kDa secretory protein of M. tuberculosis H37Rv (Mtb30; 0.1-10 mg/kg) showed enhanced levels of serum CSFs; maximum response (142 +/- 16 colonies) occurred at 1 mg/kg. In vitro, Mtb30 (1-50 mug/mL) induced mouse peritoneal macrophages (PMs) to elaborate CSFs in the conditioned medium (CM); 25 mug/mL appeared optimal (97 +/- 11 colonies). Both in vivo and in vitro, peak CSF production occurred 24 h after stimulation which levelled-off to background levels by 72 h. Rabbit anti-Mtb30 antibody significantly (p<0.05) reduced CSF production by both Mtb30-stimulated and M. tuberculosis-infected PMs, in vitro. The induced CSFs, both in the serum and CM, appeared to be functionally similar, as they supported the formation of granulocyte (G), monocyte (M) and GM colonies, in similar proportions; the GM colonies were maximum (>79 %). Neutralizing (100%) rabbit anti-mouse interleukin-1 (IL-1) polyclonal antibody did not affect the Mtb30-induced CSF production, indicating it to be IL-1-independent; whereas, CSF production was partly dependent on tumour necrosis factor-alpha (TNF-alpha), as goat anti-mouse TNF-alpha immunoglobulin G only partly inhibited it. Mtb30-induced PM production of CSFs was de novo as it was completely blocked by cycloheximide (50 mug/mL). The CSF-inducing capability of Mtb30 appeared to be proteinaceous in nature as it was heat (70 degrees C; 1 h)-labile, was destroyed by proteases (pronase E and trypsin) and was unaffected by sodium periodate treatment. Further, compared to the controls, Mtb30 induced significantly (p<0.05) high levels of immunoreactive GM-CSF (9+/-1 and 7.5+/-0.8 ng/mL) and M-CSF (4.3+/-0.5 and 3.9+/-0.4 ng/mL) in serum and CM, respectively; G-CSF levels did not increase significantly (p>0.05). Mtb30-treated mice showed a maximum of 2.23- and 2.36-fold increase, in the splenic and femur colony forming unit-GM counts, respectively, as compared to the controls. This is the first report which demonstrates Mtb30-induced production of CSFs that is up-regulated both posttranscriptionally and functionally, and thus adds to our understanding of the molecular pathogenetic mechanisms of TB.
Eur Cytokine Netw
PMID:Induction of colony-stimulating factors by a 30-kDa secretory protein of Mycobacterium tuberculosis H37Rv. 1562 42

In this work we studied the biological activities of recombinant IL-1beta from the teleosts sea bass (Dicentrarchus labrax) and rainbow trout (Oncorhynchus mykiss) by investigating the effects induced on intracellular Ca2+ concentrations ([Ca2+]i) of spleen leucocytes. Splenocytes were loaded with the Ca2+-permeant Fura-2AM, and then stimulated with rIL-1beta. The emitted fluorescence was read for 5 min at 1 min intervals on a dual excitation fluorescence fluorimeter. Results showed that rIL-1beta induced in both species a rise in [Ca2+]i, and a subsequent decrease until 5 min after stimulation. The stimulating effect was dose-dependent in both species reaching a plateau at 200 ng/ml of rIL-1beta, was abolished by heat-treatment of rIL-1beta, and affected in a dose-dependent fashion by treatment of leucocytes with trypsin. These features suggested a functional IL-1 receptor was involved in the binding. The observed rise in [Ca2+]i was not detected in human PBMC and was species-specific, since rIL-1beta from sea bass, trout, and human were unable to interfere each other in the assay. Moreover, incubation of splenocytes with rIL-1beta induced a rapid tyrosine phosphorylation of a 24 kDa polypeptide in both species. This work represents the first evidence of a direct effect on [Ca2+]i induced by IL-1beta and suggests that in the evolution of IL-1 activities, teleost fishes display a peculiar IL-1-associated behaviour that is lacking in mammals.
Cytokine 2006 Apr
PMID:Evolution of cytokine responses: IL-1beta directly affects intracellular Ca2+ concentration of teleost fish leukocytes through a receptor-mediated mechanism. 1671 84

Treatment of primary keratinocytes (HEKAp) with trypsin led to the production and release of CXCL8. Production of CXCL8 was exquisitely sensitive to inhibition by co-treatment with the beta(2) agonist sabutamol (IC(50)=1.1 nM). The inhibitory effect of salbutamol was beta receptor-mediated since the effect was prevented by the beta antagonist sotalol. Salbutamol also elevated intracellular levels of cAMP (EC(50)=82 nM) but the relationship to the inhibition of CXCL8 secretion was not clear-cut since much higher concentrations of salbutamol were required to elevate total cellular cAMP than inhibit CXCL8 production. However, the effect of salbutamol is likely to be mediated by elevation of cAMP since forskolin, an adenylyl cyclase activator, mimicked the effects of salbutamol while the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine inhibited the effects of salbutamol. Potentiation of cAMP production by co-treatment with the phosphodiesterase type 4 inhibitor rolipram only marginally enhanced the inhibitory effect of salbutamol on CXCL8 production. Taken together, these data suggest that elevation of cAMP production is required for the inhibitory effect of salbutamol on CXCL8 production by keratinocytes and that low threshold levels of cAMP are sufficient to mediate this effect.
Cytokine 2006 Oct
PMID:Salbutamol inhibits trypsin-mediated production of CXCL8 by keratinocytes. 1716 17

GM-CSF has been showed to be able to induce up-regulated receptor and cytokine expression in mast cells in inflammatory conditions. However, little is known of its effects on protease activated receptor (PAR) expression and Th2 cytokine secretion from mast cells. In the present study, we examined potential influence of GM-CSF on mast cell PAR expression and IL-4 and IL-10 release by using flow cytometry analysis, quantitative real time PCR, ELISA and cellular activation of signaling ELISA (CASE) techniques. The results showed that GM-CSF induced up to 3.0-fold increase in IL-4 release from P815 cells, and FSLLRY-NH(2) and trans-cinnamoyl (tc)-YPGKF-NH(2) did not affect GM-CSF induced IL-4 release. GM-CSF reduced tryptase and trypsin induced IL-4 release by up to approximately 55.8% and 70.3%, respectively. GM-CSF elicited the upregulated expression of PAR-1, PAR-2, PAR-3 and PAR-4 mRNAs, but enhanced only PAR-4 protein expression in P815 cells. U0126, PD98059 and LY204002 almost completely abolished GM-CSF induced IL-4 release when they were preincubated with P815 cells for 30 min, indicating ERK and Akt cell signaling pathways may be involved in the event. In conclusion, GM-CSF can stimulate IL-4 release from mast cells through an ERK and Akt cell signaling pathway dependent, but PAR independent mechanism. GM-CSF may serve as a regulator for IL-4 production in mast cells and through which participates in the mast cell related inflammation.
Cytokine 2009 Dec
PMID:Induction of IL-4 release and upregulated expression of protease activated receptors by GM-CSF in P815 cells. 1965 24

Parachlamydia acanthamoebae is a Chlamydia-related organism whose pathogenic role in pneumonia is supported by serological and molecular clinical studies and an experimental mouse model of lung infection. Toll-like receptors (TLRs) play a seminal role in sensing microbial products and initiating innate immune responses. The aim of this study was to investigate the roles of MyD88, TLR2, and TLR4 in the interaction of Parachlamydia with macrophages. Here, we showed that Parachlamydia entered bone-marrow derived macrophages (BMDMs) in a TLR-independent manner but did not multiply intracellularly. Interestingly, compared to live bacteria, heat-inactivated Parachlamydia induced the production of substantial amounts of tumor necrosis factor alpha (TNF), interleukin-6 (IL-6), and IL-12p40 by BMDMs and of TNF and IL-6 by peritoneal macrophages as well as RAW 264.7 and J774 macrophage cell lines. Cytokine production by BMDMs, which was partially inhibited upon trypsin treatment of Parachlamydia, was dependent on MyD88, TLR4, and, to a lesser extent, TLR2. Finally, MyD88(-/-), TLR4(-/-), and TLR2(-/-) mice were as resistant as wild-type mice to lung infection following the intratracheal instillation of Parachlamydia. Thus, in contrast to Chlamydia pneumoniae, Parachlamydia acanthamoebae weakly stimulates macrophages, potentially compensating for its low replication capacity in macrophages by escaping the innate immune surveillance.
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PMID:Role of MyD88 and Toll-like receptors 2 and 4 in the sensing of Parachlamydia acanthamoebae. 2083 14

RANTES is a potent chemoattractant for various important inflammatory cells such as eosinophils, memory T cells and mast cells. It has been long recognized as a crucial player in the pathogenesis of allergy. However, little is known of its effects on cytokine secretion and protease activated receptor (PAR) expression in mast cells. In the present study, we examined potential influence of RANTES on IL-13 and IL-12 release from P815 cells and PAR expression on P815 cells by using flow cytometry analysis, quantitative real-time PCR, ELISA and cellular activation of signaling ELISA (CASE) techniques. The results showed that RANTES induced up to 2.2-fold increase in IL-13, but not IL-12 release from P815 cells. Blocking antibodies against RANTES and CCR5 diminished RANTES induced IL-13 release. Furthermore, RANTES upregulated expression of PAR-1, PAR-2 and PAR-3 mRNAs, but enhanced only PAR-1 protein expression. At 1 ng/ml, RANTES can abolish tryptase induced IL-13 release, but enhance trypsin, tryptase and thrombin induced PAR-1, -2 and -4 expression. LY204002 abolished RANTES induced IL-13 release, indicating an Akt cell signaling pathway may be involved in the event. In conclusion, RANTES can stimulate IL-13 release from mast cells through a CCR5 and Akt cell signaling pathway dependent mechanism. It can also enhance trypsin, tryptase and thrombin-induced expression of PARs in mast cells. RANTES may contribute to modulation of IL-13 production and PAR expression in mast cells, through which participates in the mast cell related inflammation.
Cytokine 2011 Feb
PMID:Induction of IL-13 production and upregulated expression of protease activated receptor-1 by RANTES in a mast cell line. 2107 54


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