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)

In the present study we have evaluated the effect of recombinant human fibroblast, IFN-beta ser, and immune, IFN-gamma, interferon, alone and in combination, on the proliferation of fifteen early passage human glioblastoma cell cultures. Explant cultures were established from glioblastoma tumor tissue obtained at the time of surgery. After sufficient outgrowth, cultures were dispersed with trypsin/versene and maintained as independent cell lines. IFN-beta ser induced a greater than or equal to 50% reduction in the 7 day growth of 6 of the 15 cultures. The majority of cultures, 9 of 15, displayed less than or equal to 50% growth suppression in comparison with control cultures after 7 days exposure to 2000 Units/ml of IFN-beta ser. When treated with 2000 Units/ml of IFN-gamma, only 1 of the 15 glioblastoma cultures exhibited a greater than or equal to 50% reduction in growth. In contrast, when treated with the combination of IFN-beta ser plus IFN-gamma, 1000 Units/ml of each interferon preparation, 12 of 15 cultures were inhibited by greater than or equal to 50% after 7 days growth. The combination of interferons was effective in suppressing glioblastoma growth both in cultures displaying relative sensitivity and those exhibiting innate resistance to either or both types of interferon when employed alone. One glioblastoma culture, G-7, was studied through 45 passages and displayed the same sensitivity at different passages to growth inhibition when exposed to IFN-beta ser, IFN-gamma or both interferons. Based on previous clinical studies indicating that IFN-beta or IFN-gamma when administered alone to patients do not generally alter the clinical progression of malignant gliomas, the present results suggest that the combination of IFN-beta plus IFN-gamma may prove more effective than either agent alone in the clinical treatment of patients with glioblastoma multiforme.
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PMID:Enhanced in vitro growth suppression of human glioblastoma cultures treated with the combination of recombinant fibroblast and immune interferons. 283 97

Purified mouse interferon gamma (MuIFN-gamma), a lymphokine having potent antiviral, immunomodulatory, and growth inhibitory activities, is internalized (t1/2 less than 1.0 min) by mouse L929 fibroblasts via receptor-mediated endocytosis. Individual MuIFN-gamma molecules, identified by a postembedding immuno-gold technique, are then transported to the cell nucleus, perhaps through nuclear pores, into areas of dense chromatin. Purified, isolated nuclei of L929 cells bind radiolabeled MuIFN-gamma specifically and with high affinity (Kd = 2 X 10(-10) M). These nuclear membrane receptors, distinct from those for MuIFN-beta, number about 24,000/nucleus. Treatment of nuclei with trypsin prevents binding of MuIFN-gamma. The demonstration of rapid cellular uptake and transport of MuIFN-gamma into the dense chromatin, perhaps facilitated by nuclear receptors, suggests that IFN-gamma molecules, alone or bound to receptor, may directly affect genome regulation.
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PMID:Transport of gamma-interferon into the cell nucleus may be mediated by nuclear membrane receptors. 294 74

Monocytes isolated from human blood by centrifugal elutriation exhibited little ability to ingest rabbit erythrocytes (ER), zymosan particles, or desialated sheep erythrocytes. In contrast, 85 to 95% of these cells rosetted with C3b- or C3bi-bearing sheep erythrocytes (ES) or ingested IgG-coated ES. Preincubation of the monocytes with human lymphocytes increased their ability to ingest ER. the ER phagocytosis-inducing activity was contained in the 105,000 X G supernatant of lymphocyte lysates. These supernatants increased the percentage of ingesting monocytes from 5 to 15% to 80% within 60 min. The soluble factor was found to be relatively heat stable, inactivated by trypsin, and distinct from IFN-gamma. Its m.w. is less than 13,000. It was present in B and T lymphocytes and also in U937 cells. These results suggest that the ability of human monocytes to ingest nonopsonized particulate activators of the alternative complement pathway is a cytokine-inducible property and that the effect of the cytokine on complement receptor- or Fc receptor-dependent adherence or ingestion of opsonized particles is minor.
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PMID:Phagocytosis by human monocytes of unopsonized particulate activators of the human alternative complement pathway: induction by cytokine. 308 15

Natural human interferon gamma(IFN-gamma) was purified from the conditioned medium of peripheral blood leukocytes using selective silica gel adsorption and antibody-affinity chromatography. SDS-PAGE and Western blot analysis demonstrated three major species with molecular masses of 25 kDa, 20 kDa and 17 kDa. Structural analysis of this natural IFN-gamma preparation demonstrated a pyroglutamate residue at the amino terminus and a heterogeneous carboxyl terminus. The longest and most predominant polypeptide was 138 amino acids in length, which is five residues shorter than the sequence predicted from the cDNA. The presence of multiple-carboxyl-terminal forms indicated possible proteolytic processing during induction or protein purification. Limited proteolytic digestion of full-length recombinant IFN-gamma with endoproteinase Lys-C and trypsin revealed that the carboxyl-terminal 15 residues could be released under conditions in which the core portion of the polypeptide chain remained intact. Thus, the heterogeneity of natural IFN-gamma may be explained by partial proteolytic degradation of the molecule and differences in the degree of glycosylation as previously reported [Rinderknecht, E., O'Conner, B. H. & Rodriguez, H. (1984) J. Biol. Chem. 259, 6790-6797].
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PMID:Structural characterization of human interferon gamma. Heterogeneity of the carboxyl terminus. 310 13

Culture supernatants of splenic T cells from susceptible CBA mice chronically infected with Trypanosoma cruzi contain a suppressive substance which can inhibit the induction of delayed-type hypersensitivity (DTH) to a wide range of antigens. The suppressive substance is distinct from T. cruzi antigen inasmuch as the supernatant depleted of any residual T. cruzi antigen by an affinity column still retains the suppressive activity, whereas addition of T. cruzi antigens to control supernatant did not confer suppressive function. The suppressive supernatant does not contain detectable levels of IL-1, IL-2, IL-3, or IFN-gamma but a modest level of IL-1 and IL-2 inhibitory activities. However, both these inhibitory activities elute at a different position from the DTH suppressive activity on gel filtration. The DTH suppressive activity is heat labile (1 h, 56 degrees C), cryostable, but destroyed by trypsin treatment. It binds to ricin but not to lentil lectin. Sepharose 4B gel filtration and HPLC analysis in mild chaotropic agents (urea, ethylene glycol) demonstrate that the suppressive substance has an apparent Mr of 30 to 60 kDa, but full DTH-suppressive activity is retained only in an aggregated form.
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PMID:Suppressive substance produced by T cells from mice chronically infected with Trypanosoma cruzi. II. Partial biochemical characterization. 312 53

This study was performed to determine the effect of Pseudomonas aeruginosa on gamma interferon (IFN-gamma) production by antigen-stimulated human T-cell clones. Crude bacterial filtrates prepared from certain strains of P. aeruginosa inhibited IFN-gamma production by T cells and reduced the antiviral activity of preformed IFN-gamma. Bacterial filtrates prepared from mutant strains that did not produce the exoenzyme alkaline protease (AP) did not inhibit IFN-gamma activity. The inhibitory activity of bacterial filtrates was heat and trypsin sensitive and was neutralized by an antiserum to AP. Crystalline AP mimicked the effects of the bacterial filtrates, and an inactive filtrate from a protease-deficient mutant strain was reconstituted by the addition of AP. AP-treated recombinant IFN-gamma showed altered migration on Western blots (immunoblots) of polyacrylamide gels, and this modification correlated with a dose-dependent loss of antiviral activity. The ability of recombinant IFN-gamma to elevate the expression of Fc receptors on cells of the U-937 histiocytic cell line was also diminished by AP treatment. These results indicate that the Pseudomonas protease AP can inhibit the antiviral and immunomodulatory activities of IFN-gamma.
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PMID:Pseudomonas aeruginosa alkaline protease degrades human gamma interferon and inhibits its bioactivity. 313 65

Supernatants from PHA-activated human peripheral blood mononuclear cells, depleted of virtually all IL-2 activity by an anti-rIL-2 immunoadsorbent column, contain a factor(s) which synergizes with rIL-2 in facilitating the generation of allogeneic human CTL responses in vitro. This factor, provisionally termed CTL maturation factor (TcMF), did not appear to promote CTL responses in the absence of rIL-2. Furthermore, it acted later than IL-2 in facilitating CTL responses and could not be replaced by recombinant IFN-gamma. In this report we show that rIFN-alpha, rIL-1 alpha, and rIL-1 beta likewise lack TcMF activity. The TcMF activity in lymphokine-containing culture supernatants could be eliminated by trypsin or pronase but not by neuraminidase or RNase. Gel filtration revealed two peaks of TcMF activity, one at 12,000 to 25,000 Da and the other at 45,000 to 65,000 Da. Isoelectrofocusing demonstrated substantial charge heterogeneity. The majority of TcMF activity was recovered between pI 4.0 and pI 5.5 with a minor component at pI 6.5, corresponding to the areas in which IL-1 activity was also found. However, TcMF activity could be separated from IL-1 by reverse-phase HPLC. Moreover, TcMF recovered following reverse-phase HPLC was also found to be depleted of IL-4 activity. These studies suggest that TcMF activity is mediated by a protein(s) distinct from IL-1, IL-2, IL-4, and interferon-alpha or-gamma.
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PMID:Characterization of a factor(s) which synergizes with recombinant interleukin 2 in promoting allogeneic human cytolytic T-lymphocyte responses in vitro. 327 3

Serum specimens from mice treated orally with Ge-132 (100 mg/kg) exhibited antitumor activity against Ehrlich (allogeneic) and RL 1 (syngeneic) ascites tumors in BALB/c mice. Sera obtained from mice 24 hours after Ge-132 administration displayed the highest antitumor effect and the antitumor activity was dose-dependent. Sera prepared from mice 12, 36 or 48 hours after Ge-132 treatment had no protective effect. Circulating interferon (IFN) was induced at 24 hours after administration. The antiviral activity of serum from Ge-132-treated mice was inactivated by treatment with trypsin, low pH, and anti-IFN-gamma antiserum. The inactivated preparations of serum IFN induced by Ge-132 did not show antitumor activity when administered to mice bearing Ehrlich ascites tumors. These results suggest that the antitumor activity in the sera of Ge-132-treated mice may have been expressed through IFN-gamma which was induced by Ge-132.
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PMID:[Ability of sera from mice treated with Ge-132, an organo-germanium compound, to inhibit experimental murine ascites tumors]. 393 51

An inhibitor of interferon action has been identified which is present in IFN-gamma preparations. The inhibitor is produced following rising interferon concentrations in mitogen stimulated mouse spleen cell cultures. Indications are that the inhibitor is produced in response to the production of interferon, and may therefore be a feedback control mechanism for the interferon system. The action of the inhibitor is independent of both interferon type and concentration, and seems to act by preventing the establishment of the interferon-induced antiviral state at some point following the interaction of the interferon molecule with the cell membrane. The inhibitor has an apparent molecular weight of 8,000 to 10,000 daltons and is stable to treatment with low pH, heat, and trypsin. It is proposed that the inhibitor has the specific role in vivo of controlling interferon-mediated activities.
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PMID:Control of the interferon system: an inhibitor of interferon action. 629 94

Moderate titres of antiviral activity were demonstrated in 48-58% of sera obtained from patients suffering from seropositive and seronegative rheumatoid arthritis (RA), psoriatic arthritis, Reiter's syndrome, ankylosing spondylitis, and juvenile rheumatoid arthritis. Sera from blood donors and from patients with various noninflammatory diseases were positive in 16% of cases. The activity was species-specific, mediated by the homologous cells, and destroyed by treatment with trypsin and exposure to pH 2. Antibodies against human IFN-alpha did not neutralise the activity. These characteristics are compatible with those of IFN-gamma or immune interferon. Neither the presence nor the titre of IFN was correlated with disease activity defined by concentration of C-reactive protein, C3 concentration, and erythrocyte sedimentation rate. IFN-gamma was present in 4 of 10 synovial fluids from patients with RA. The titre in one of these was higher than in the corresponding serum, indicating local production in the rheumatoid joint.
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PMID:Immune interferon in serum and synovial fluid in rheumatoid arthritis and related disorders. 641 86


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