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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies have suggested that recombinant tumor necrosis factor-alpha (TNF-alpha) may potentiate the killing of murine tumor cells by drugs targeted at DNA topoisomerase II. We have examined the combined cytotoxic effects of the topoisomerase-targeted drug etoposide and TNF in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cell lines using clonogenic assays and a novel flow cytometry technique relying on differential uptake of fluorescein diacetate (FDA) and propidium iodide (PI) by viable and nonviable cells. Good correlation of IC50 determinations for etoposide were noted between clonogenic assays and the FDA/PI technique for both classic and variant SCLC cell lines. The effects of etoposide on the classic SCLC line H209 were potentiated by TNF with a decrease in the IC50 from 3.3 microM to 1.0 microM as determined by FDA/PI. Tumor necrosis factor alone had little effect on the growth or cloning efficiency of H209 cells. Tumor necrosis factor alone stimulated the growth and cloning of variant SCLC line N417, but the cytotoxicity of etoposide was not potentiated by TNF in N417 cells. Tumor necrosis factor alone inhibited the growth and cloning of the NSCLC line H125 but exerted a marked protective effect against higher concentrations of etoposide. It appears that the interaction of TNF with etoposide varies between cell lines and between subclasses of human lung cancer.
Mol Biother 1990 Sep
PMID:Interaction of recombinant human tumor necrosis factor and etoposide in human lung cancer cell lines. 217 61

Interleukin-6 (IL-6) modulates a number of processes relevant to host immunity and inflammation. We investigated the capacity of the human alveolar macrophage to elaborate IL-6 in response to lipopolysaccharide (LPS), recombinant interleukin-1 (rIL-1), and recombinant tumor necrosis factor (rTNF), and compared macrophage IL-6 production to that of blood monocytes and lung fibroblasts. Unstimulated and TNF-stimulated alveolar macrophages and monocytes produced little or no detectable IL-6. In contrast, macrophages and monocytes produced large amounts of IL-6 in response to LPS and monocytes produced lesser but readily detectable amounts in response to rIL-1. Monocytes and alveolar macrophages differed significantly in their capacity to produce IL-6, with macrophages making more IL-6 in response to LPS and less IL-6 in response to rIL-1 than autologous blood monocytes. Monocytes aged in vitro produced little detectable IL-6 in response to LPS or rIL-1, suggesting that differences in cell maturity may account for the diminished capacity of the alveolar macrophage to produce IL-6 in response to IL-1 but not its enhanced capacity to produce IL-6 in response to LPS. Mononuclear phagocytes and lung fibroblasts also differed in their ability to produce IL-6. Lung fibroblasts produced more IL-6 in response to rIL-1 and less IL-6 in response to LPS than monocytes and macrophages. In addition, monocytes and macrophages elaborated electrophoretically identical IL-6 moieties that differed from those produced by lung fibroblasts. These differences could be at least partially attributed to differences in sialylation and/or glycosylation.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1990 Nov
PMID:Human alveolar macrophage and blood monocyte interleukin-6 production. 222 4

We determined whether normal human lung fibroblasts expressed cell-associated thymocyte-stimulating activity in response to recombinant interleukin-1 (rIL-1) (alpha and beta) and recombinant tumor necrosis factor (rTNF). Individually, rIL-1 and rTNF induced fibroblast expression of thymocyte-stimulating activity, with rIL-1 being significantly more potent. Importantly, combining rIL-1 and rTNF resulted in a synergistic increase in fibroblast thymocyte-stimulating activity. This synergistic interaction was dose dependent for both cytokines and was not noted when gamma-interferon was combined with rIL-1 or rTNF. In all cases, the thymocyte-stimulating activity was the result of an IL-1 alpha-like moiety whose maximal production required protein synthesis. IL-1 alpha activity could be detected after as little as 4 h, peaked after 24 h, and returned toward normal with longer periods of cytokine-fibroblast incubation. However, cytokine-stimulated fibroblasts that no longer expressed IL-1 alpha activity could be induced to re-express this activity with repeat cytokine challenge. Induction of fibroblast IL-1 alpha by IL-1 and/or TNF may be an important mechanism amplifying IL-1-mediated biologic events at sites of local inflammation.
Am J Respir Cell Mol Biol 1990 Jul
PMID:Interleukin-1 and tumor necrosis factor synergistically stimulate lung fibroblast interleukin-1 alpha production. 236 34

Granulocyte (G) and granulocyte-macrophage (GM) colony-stimulating factors (CSF) are necessary for proliferation and differentiation of myeloid hematopoietic cells. Fibroblasts stimulated by tumor necrosis factor alpha (TNF alpha) and several other agents are a rich source of these CSF. The GM-CSF synthesized by these cells had the same molecular weight and glycosylation pattern as that produced by activated T lymphocytes, as shown by [35S]methionine labeling studies. Northern (RNA) blot analysis showed that the fibroblasts had trace levels of G- and GM-CSF mRNA. Both G- and GM-CSF mRNA concentrations coordinately increased after exposure of the cells to TNF alpha (greater than or equal to 5 ng/ml), 12-O-tetradecanoylphorbol 13-acetate (TPA) (greater than or equal to 5 x 10(-10) M), or cycloheximide (20 micrograms/ml). Both TNF alpha and TPA increased levels of G- and GM-CSF mRNA in the absence of new protein synthesis. Transcriptional run-on studies demonstrated that fibroblasts constitutively transcribed GM-CSF, and transcription was enhanced 3.0-fold by TNF alpha and 2.5-fold by TPA and was unchanged by cycloheximide. The stability of G- and GM-CSF transcripts was determined after exposure of the cells to actinomycin D; the half-lives of G- and GM-CSF mRNA in unstimulated cells were less than 0.25 h and were increased 2- to 16-fold in cells cultured with TNF, TPA, or cycloheximide. In summary, both transcriptional and posttranscriptional signals acted coordinately to modulate the levels of G- and GM-CSF mRNAs in fibroblasts.
Mol Cell Biol 1988 Aug
PMID:Transcriptional and posttranscriptional modulation of myeloid colony-stimulating factor expression by tumor necrosis factor and other agents. 246 77

Analysis of 53 somatic cell hybrids between TNF-sensitive myeloid cells (U937) and TNF-resistant T-cell lines HUT78 (UH-hybrids) and Jurkat (UJ-hybrids), respectively, revealed complete resistance to TNF-mediated cytostasis in all cases. Moreover, all hybrids remained insensitive to a combined treatment with TNF-alpha and IFN-gamma, which exert synergistic growth inhibition and cytotoxicity on parental U937 cells. Analyses of cell surface marker expression, membrane phosphoproteins, and expression of tissue-specific cytokine genes revealed differential conservation of myeloid and T-cell-specific properties in each of these hybrids, but invariant, dominant resistance to TNF-alpha-mediated growth inhibition. All TNF-resistant hybrids expressed a membrane phosphoprotein pattern, which closely resembled that of the respective parental T-cell lines. In particular, two membrane phosphoproteins of apparent molecular weight of 50,000 and 38,000 were common in the two parental T-cell lines and all UH- and UJ-hybrid clones, suggesting a possible role of these proteins in mediating TNF resistance.
Mol Biother 1988
PMID:Mechanisms of TNF resistance: identification of membrane phosphoproteins associated with a dominant resistant phenotype in lymphoid-myeloid somatic cell hybrids. 247 98

Genes, coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta), have been cloned from the rabbit genomic library. The two genes are tandemly arranged and separated only by 1 kb of DNA as previously observed in human and mouse genomes. We have sequenced the entire rabbit lymphotoxin gene (LT) and calculated the amino acid sequence of the rabbit LT whose cDNA is not yet cloned. We also analyzed the upstream sequences of this gene and revealed a number of recognition sites for the known transcriptional factors. The rabbit TNF gene comprised in the cloned genomic region has been sequenced earlier.
Mol Biol (Mosk)
PMID:[Cloning and structural analysis of genes coding for tumor necrosis factor and lymphotoxin in rabbits]. 263 43

The macrophage-derived lymphokine interleukin 1 (IL 1) plays a critical role in modulating immune (cellular and humoral) and nonimmune responses. For example, the relative expression of IL 1 alpha and beta under various states may be crucial to the success of the immune system in response to infection. Until recently, a comparative study of IL 1 mRNA expression and IL 1 biological activity was not possible. We have cloned both IL 1 alpha and beta cDNAs and employed them as probes in Northern blot analysis to determine in mitogen-stimulated peripheral blood mononuclear cells the steady-state expression of their cognate mRNAs with respect to IL 1 activity. IL 1 was determined by the lymphocyte-activating factor (IL 1/LAF) and the mononuclear cell factor (IL 1/MCF) activities. In lectin-stimulated PBMC, maximum cell-associated activities whereas detected at 12 and 24 hr after stimulation whereas maximum extracellular activities appeared between 24-48 hr. In the same cultures, the kinetics of IL 1 mRNA steady-state expression were determined by Northern gel blot analysis with IL 1 alpha and beta cDNA probes. IL 1 mRNAs were undetectable in noncultured freshly isolated PBMC (time zero). Both IL 1 mRNAs appeared as early as 4 hr after lectin stimulation as did IL 1 beta mRNA in unstimulated cultures. Both IL 1 alpha and beta mRNA steady-state levels were barely detectable by 48 hr. At all time points, IL 1 mRNA levels were considerably lower in unstimulated cultures. IL 1 beta mRNA was always considerably more abundant than IL 1 alpha mRNA. The less abundant IL 1 alpha mRNA showed a decrease in its stead-state levels prior to the reduction in the levels of IL 1 beta mRNA. TNF alpha activity and mRNA were not detected under these culture conditions. Poly(A) + RNA injected into Xenopus oocytes revealed that the Northern blot detected IL 1 mRNAs were biologically active. To understand the precise nature of IL 1 in immune and nonimmune events, we felt it necessary to first study the kinetics of IL 1 mRNA steady-state levels with respect to its cell-associated and extracellular biological activities. The data presented here may allow for a better understanding of the etiology of various immune and nonimmune responses that are modulated through the expression of IL 1.
J Mol Cell Immunol 1987
PMID:Expression of human IL 1 alpha and beta messenger RNAs and IL 1 activity in human peripheral blood mononuclear cells. 350 26

TNF alpha and IL-1 each can activate NF-kappa B and induce gene expression of manganese superoxide dismutase (MnSOD), a mitochondrial matrix enzyme which can provide critical protection against hyperoxic lung injury. The regulation of MnSOD gene expression is not well understood. Since redox status can modulate NF-kappa B and potential kappa B site(s) exist in the MnSOD promoter, the effect of thiols (including NAC, DTT and 2-ME) on TNF alpha and IL-1 induced activation of NF-kappa B and MnSOD gene expression was investigated. Activation of NF-kB and increased MnSOD expression were potentiated by thiol reducing agents. In contrast, thiol oxidizing or alkylating agents inhibited both NF-kappa B activation and elevated MnSOD expression in response to TNF alpha or IL-1. Since protease inhibitors TPCK and TLCK can inhibit NF-kappa activation, we also investigated the effect of these compounds on MnSOD expression and NF-kappa B activation. TPCK and TLCK each inhibited MnSOD gene expression and NF-kappa B activation. Since the MnSOD promoter also contains an AP-1 binding site, the effect of thiols and thiol modifying agents on AP-1 activation was investigated. Thiols had no consistent effect on AP-1 activation. Likewise, some of the thiol modifying compounds inhibited AP-1 activation by TNF alpha or IL-1, whereas others did not. Since diverse agents had similar effects on activation of NF-kappa B and MnSOD gene expression, we have demonstrated that activation of NF-kappa B and MnSOD gene expression are closely associated and that reduced sulfhydryl groups are required for cytokine mediation of both processes.
Mol Cell Biochem 1995 Jul 05
PMID:Thiol modulation of TNF alpha and IL-1 induced MnSOD gene expression and activation of NF-kappa B. 747 33

In porcine heart, embolization of small coronary arteries with microspheres in 25 microns in diameter induces collateral capillary vessel growth by angiogenesis in and around focal necrosis. By histological analysis the inflammatory infiltrates in this porcine tissue were characterized by numerous monocytes/macrophages and fibroblasts as well as neutrophils and numerous capillaries, some in mitosis. The aim of the present study, therefore, was to clarify the role of monocytes/macrophages and fibroblasts in angiogenesis and in repair in ischemic porcine myocardium. Using a human acidic fibroblast growth factor (aFGF) cDNA probe for in situ hybridisation labeling for aFGF mRNA was seen in monocytes and macrophages only, beginning at day 1, with a maximum at 3 and 7 days, and minimal labeling at 4 weeks. We have also shown, with a specific antibody and fluorescence microscopy, that tumur necrosis factor alpha (TNF alpha) follows the same time sequence and that it is produced by monocytes/macrophages. The number of capillaries in infiltrates at 3 and 7 days as revealed by the lectin Dolichus Biflorus Agglutinin was high and declined at 4 weeks. In situ hybridisation using a rat cDNA probe for fibronectin showed the increased production of fibronectin mRNA in fibroblasts. To describe the expression of fibronectin and the collagens I, III, VI immunohistochemistry was used. A comparison showed that fibroblasts produced fibronectin mRNA starting at day 3, but the protein was only maximally expressed at day 7 and 4 weeks. Collagen I, III, VI expression was highest at 1-4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem
PMID:Importance of monocytes/macrophages and fibroblasts for healing of micronecroses in porcine myocardium. 749 42

Albumin-like glycoprotein (Gp66) with a molecular mass of 66 kDa has been isolated from human fetal tissue by size-exclusion, ion-exchange chromatography and reverse-phase HPLC. Reactivity of Gp66 with antiserum raised against the major protein components fraction of human fetal serum was observed. The N-terminal 35 amino acid residues of Gp66 were identical to human serum albumin. Meanwhile Gp66 differed from albumin by a/ the presence of 3-5 Trp residues instead of 1 according to fluorescence and UV-spectra, b/ the glycosylation pattern: bi-, tri-, and tetraantennary sialooligosaccharides of a complex type were present. Isoelectric focusing revealed 4 isoforms (pI ranging within 4.8 to 5.1) of Gp66. Gp66 (but not asialo-Gp66) was able to inhibit the cytotoxic effect of TNF against the tumor cell line L929. Inhibition of WEHI-3 and L929 tumor cells proliferation by Gp66 was similar to that of albumin.
Biochem Mol Biol Int 1994 May
PMID:Albumin-like glycoprotein from human fetal tissue. 752 4


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