Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:017444 (TNF)
 61,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor alpha mediated cell death in L929 cells correlates with a late increase in reduction of the superoxide scavenger 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), suggesting an increase in MTT reduction per viable cell. This effect was studied in two TNF-sensitive and in five different TNF-resistant clones. Within 36 hrs TNF promoted a 7-fold increase in the reduction of MTT in TNF-sensitive cells. Exogenous ceramide induced a similar effect prior to cell death. Four of the five TNF-resistant clones were also resistant to ceramide and displayed no increase in MTT reduction with either TNF or ceramide. The remaining TNF-resistant clone was sensitive to ceramide, displaying an increase in MTT reduction. Our results suggest a late increase in superoxide production prior to cellular destruction during TNF and ceramide mediated cell death and support the notion that ceramide can serve as a second messenger for TNF in cell death.
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PMID:Ceramide reproduces late appearance of oxidative stress during TNF-mediated cell death in L929 cells. 892 Sep 43

The effects of the mycotoxin cyclopiazonic acid (CPA) on cytokine secretion and gene expression were evaluated in the WEHI-3 murine macrophage cell line. Lipopolysaccharide (LPS)-stimulated and non-stimulated cells were exposed to various concentrations of CPA and culture supernatants were assessed for interleukin (IL)-1 beta, IL-6 and TNFalpha by ELISA. Without LPS stimulation, only IL-6 was increased by CPA at 5000 ng/ml after 1, 2 and 3 days. With LPS stimulation, IL-1 beta was elevated in the presence of 500 and 1000 ng/ml of CPA at 1 day and 500, 1000 and 5000 ng/ml at 2 days and 3 days. TNF alpha was increased by 1000 ng/ml CPA at 12 h and by 500, 1000 and 5000 ng/ml CPA at 1-3 days. IL-6 levels were increased in the presence of 100, 500 and 1000 CPA ng/ml at both 12 h and 3 days and in the presence of 100, 500, 1000 and 5000 ng/ml CPA at both 1 day and 2 days. The cytokine effects were further related to proliferation and cell viability using the MTT [3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide] assay. Proliferation was increased relative to controls in the presence of 50-1000 ng/ml of CPA in LPS-stimulated cells and in the presence of 500-1000 ng/ml CPA in unstimulated cells. In contrast, proliferation was markedly inhibited by 5000 ng/ml CPA in both stimulated and unstimulated cells. To relate the effect of CPA on IL secretion to mRNA transcript levels, LPS-stimulated cells were incubated with 1000 ng/ml of CPA for 2, 4, 8, 12 and 24 h and cytokine mRNA levels were evaluated using RT-PCR in combination with Southern hybridization analysis. In the presence of LPS only, IL-1 beta and IL-6 mRNA peaked at 8 h and 4 h, respectively, and then decreased whereas TNF alpha mRNA was strongly expressed from 2-8 h and markedly decreased at 12 h. In the presence of LPS and CPA, however, IL-1 beta and IL-6 mRNA levels gradually increased up to 24 h reaching 2.5 and 29-fold higher than controls, respectively. In contrast, TNF alpha mRNA levels slowly decreased after 8 h but remained markedly elevated relative to controls. Taken together, these results suggest that CPA can superinduce both secretion and mRNA levels of proinflammatory cytokines associated with macrophage activation. Cytokine upregulation was not always consistent with proliferative effects.
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PMID:Increased IL-1, IL-6 and TNF alpha secretion and mRNA levels in WEHI-3 cells exposed to cyclopiazonic acid. 893 62

The effects of mast cells (MCs) isolated from rat peritoneal cavity on rat hepatoma cell line (CBRH7919) in vitro were studied with phase contrast microscopy, scanning and transmission electron microscopy. The results showed that different degrees of degeneration were present in all CBRH7919 cells and a few of them exhibited necrosis or disruption when CBRH7919 cells were cocultured with MCs for 24 hours. In situ hybridization demonstrated that the expression of c-myc mRNA in CBRH7919 cells was markedly reduced by MCs. MTT colorimetric assay indicated that the supernatants of MC cultures had suppressive effect on the proliferation of CBRH7919. A monoclonal anti-mouse TNF antibody could decrease the suppressive effect. These results suggest that MCs had anti-tumor effect.
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PMID:[Studies of mast cell-mediated cytotoxicity to hepatoma cells in vitro]. 938 20

Adoptive transfer of activated autologous human macrophages obtained by in vitro differentiation of monocytes in culture has successfully undergone phase I clinical trials in patients with metastatic cancer. The efficacy of these autologous macrophages in the in vivo killing of human tumors has now to be demonstrated. GM-CSF was shown to increase the number of monocytes differentiating in culture into macrophages. These were then activated with IFN gamma which was reported as the best cytokine for tumoricidal activation of macrophages. The aim of this paper was to evaluate the in vitro tumoricidal activity of macrophages grown with GM-CSF and IFN gamma. This tumoricidal function was investigated by measurement of the cytolytic (chromium-51 release assay), cytostatic (anti-proliferative activity as measured by inhibition of [3H]-thymidine incorporation in two different assays) and cytotoxic (MTT assay) activities on two tumor cells lines, U937 and K562 (respectively highly sensitive and resistant to soluble TNF alpha). Our results demonstrated that GM-CSF-grown macrophages exhibited significant cytolytic, cytotoxic and cytostatic activities on U937 cells. These were partly enhanced by IFN gamma activation. In contrast, they had no lytic and lower cytotoxic and cytostatic activities on K562 cells, and these were not modified by IFN gamma activation. Our data provide valuable information for future in vivo studies using adoptively transferred autologous macrophages.
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PMID:Tumoricidal potential of human macrophages grown in vitro from blood monocytes. 941 98

We investigated whether the biological response modifiers like IFN-alpha, IFN-gamma and TNF-alpha could enhance the cytotoxic action of cisplatin on cervical carcinoma cell lines in vitro. The sensitivity of three cell lines SiHa, ME 180 and C33A to these agents was tested using colorimetric MTT assay as well as tritiated thymidine uptake. All the three cell lines demonstrated range of sensitivity to cisplatin and cytokines. Interferons and TNF when used in combination with lower dose of cisplatin showed a significant enhancement of cytotoxic action of the drug in all the cell lines. Thus these data indicate that cytokines in concert with the drug may have a potential to improve the 'in vivo' therapy in these patients.
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PMID:Augmentation of cisplatin cytotoxicity using cytokines on cervical carcinoma cell lines. 1085 95

The aim of this work was to examine in vitro the ability of cells from patients with recurrent vulvovaginal candidiasis (RVVC) to cell-mediated immune response. Peripheral blood mononuclear cells (PBMC) and whole blood cells (WBC) of 37 RVVC patients in acute infection and 14 in remission were examined for the ability to proliferation and cytokines production (IFN, TNF, IL-6). As a control, a group of 25 healthy women were examined. The cells were stimulated with Candida antigen (HKCA), LPS and PHA. To indicate the level of cytokines, the following cell-lines were used: A549 for IFN, WEHI 164 for TNF and 7TD1 for IL-6. The proliferation/death of cells was determined by colorimetric test using MTT. Distinct suppression of cell-mediated immune response (CMI) was shown in all patients comparing to the control. Greatest suppression was found in the acute phase of the disease. The ability of cells to proliferate and produce IFN increases only in remission. The data seem to suggest that in this phase of disease, the ability of cell-mediated immune response is restored. It was also indicated that IFN may take part in protection against Candida infection.
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PMID:The study of cell-mediated immune response in recurrent vulvovaginal candidiasis. 1102 46

A successful pregnancy has been postulated to be the result of a discrete balance between T-helper 1 (Th1) and T-helper 2 (Th2) type cytokines involved in growth and development of the conceptus. The aim of the present study was to examine the effect of Th1 cytokines (interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha)) on the release of Th2 cytokines including IL-6 and IL-10 by trophoblast cells obtained from term placenta. Trophoblast cells isolated by enzymatic disaggregation and Percoll gradient fractionation were cultured in supplemented medium alone or with varying concentrations of the selected recombinant cytokines. After 48 h of incubation, samples of the culture supernatant were analyzed for the Th2 cytokines IL-6 and IL-10 using specific ELISA assays. Both IL-1 beta and TNF alpha had no effect on the cell number and viability as determined by MTT assay. IL-1 beta significantly stimulated trophoblast release of IL-6 in a dose-dependent manner (3.3-, 5.5-, 10.3- and 22.4-fold higher compared to the control at 10, 50, 100, 500 U IL-1 beta/ml respectively, p < 0.05). TNF alpha also stimulated release of IL-6 by these cells. However, the stimulation at lower concentrations was not very high and a significant (p < 0.05) stimulation was observed only at higher concentrations (1.1-, 1.3-, 2.6- and 5.9-fold higher at 500, 1000, 1500, 2000 U TNF alpha/ml respectively). In contrast, neither IL-1 beta or TNF alpha exerted any significant effect on IL-10 release by term trophoblast cells (p > 0.05). The results of this study provide evidence that production of Th2 cytokines might be under the control of different regulatory pathways.
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PMID:Effect of T-helper 1 cytokines on secretion of T-helper 2 cytokines by term trophoblast cells in culture. 1110 68

In order to find out the activity of NKC and production of IL-2 in the peripheral blood mononuclear cells and the level of IL-6 and TNF alpha in the peripheral blood serum, we investigated 51 herion addicts who were in the course of detoxification. MTT colorimetric assay and ELISA assay methods were adopted. The results showed that, in the herion addicts, NK activity was 30.11 +/- 5.2%, IL-2 activity was 8.06 +/- 1.66 IU/ml, IL-6 level was 61.17 +/- 12.07 pg/ml, and TNF alpha level was 91.83 +/- 19.19 pg/ml, whereas in the healthy controls, the results were 44.89 +/- 4.75%, 15.91 +/- 3.83 IU/ml, 22.18 +/- 9.31 pg/ml and 30.55 +/- 11.94 pg/ml respectively. When the herion addicts were subjected to detoxication, their NKC and IL-2 activities, IL-6 and TNF alpha levels gradually restored to normal, and were correlated with the time of their detoxification (NKC: r = 0.626, P < 0.001; IL-2: r = 0.684, P < 0.001; IL-6: r = -0.791, P < 0.001; TNF alpha: r = -0.703, P < 0.001).
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PMID:[Changes and significance of natural killer cell, IL-2, IL-6 and TNF alpha of heroin addicts after detoxification]. 1138 67

TRAIL, Tumor necrosis factor-related apoptosis-inducing ligand), a member of the TNF family, is known to be cytotoxic for a high proportion of tumor cell lines. However, successful application of TRAIL in tumor therapy may depend on finding other agents that can potentiate its antitumor effects. The present study showed that the cytostatic/cytotoxic TRAIL activity against U937 cells could be significantly augmented by proteasome inhibitor PSI, as revealed by MTT assay. Increased cytostatic/cytotoxic effect on U937 cells by TRAIL/PSI combined treatment was caused by apoptosis, as shown by an increased PARP cleavage rate. TRAIL/PSI did not affect the level of mRNA expression for TRAIL receptors (DR4, DR5, DcR1) and other apoptosis signal transduction molecules (TRADD, caspase-8).
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PMID:Augmented pro-apoptotic effects of TRAIL and proteasome inhibitor in human promonocytic leukemic U937 cells. 1139 70

The relationship between expression and function of the epidermal growth factor (EGF) family of receptors and chemosensitivity remains controversial. We studied the chemosensitivity to various anticancer agents of human cervical squamous carcinoma ME180 cells, and two resistant subclones, ME180/TNF and ME180/Pt, which also differ in their EGF receptor (EGFR) expression. Compared with ME180 cells, EGFR is overexpressed sixfold in ME180/TNF cells and is barely detectable in ME 180/Pt cells. Cell cycle analysis by flow cytometry and BrdU incorporation into DNA showed a correlation between EGFR expression and percentage of cells in S phase and active DNA replication (35% in high EGFR-expressing ME180/TNF cells, 19% in non-EGFR-expressing ME180/Pt cells and 23% in parental, intermediate-level EGFR-expressing ME 180 cells). By MTT assay and compared with parental, intermediate-level EGFR-expressing ME180 cells, high EGFR-expressing ME180/TNF cells had a three- to fourfold increased sensitivity to cisplatin, camptothecin (CPT), and topotecan, and low EGFR-expressing ME180/Pt cells had a five- to ninefold reduced sensitivity to the same agents. In contrast, the degree of cross-resistance with the topoisomerase II inhibitors doxorubicin and etoposide was minimal and the pattern of sensitivity to the anti-microtubulin agents vinblastine and paclitaxel was different, with a two- to fourfold decreased sensitivity in the high EGFR-expressing ME180/TNF cells and only a 1.5-fold decreased sensitivity in the low EGFR-expressing ME180/Pt cells. Neither alterations in intracellular CPT levels nor changes in topoisomerase I expression or activity, measured as ability to form DNA-protein complexes, were found to explain the differences in sensitivity to CPT among the three cell lines. Co-treatment with CP358774, a specific EGFR tyrosine kinase inhibitor, reduced the enhanced sensitivity of high EGFR-expressing ME180/TNF cells to the values observed in intermediate EGFR-expressing ME180 cells, but only reduced modestly the sensitivity of intermediate expressing ME180 cells. As a result, the resistance index of low EGFR-expressing ME180/Pt cells compared with intermediate EGFR-expressing ME180 cells was reduced only from five- to fourfold for cisplatin and from seven- to fourfold for CPT when ME180 cells were exposed to CP358774. CP358774 did not affect the sensitivity to either agent in low EGFR-expressing ME180/Pt cells. These results provide evidence that changes in EGFR expression or function may play a role in determining chemosensitivity to platinum and topoisomerase I poisons in some human tumor systems, and that the EGFR-related changes in chemosensitivity may vary depending on the level of EGFR expression and/or function.
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PMID:Sensitivity to topoisomerase I inhibitors and cisplatin is associated with epidermal growth factor receptor expression in human cervical squamous carcinoma ME180 sublines. 1145 99


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