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Lipopolysaccharide (LPS) and interferon-γ (IFN-γ) induced nitric oxide synthase (NOS) activity, tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and prostaglandin (PG)E 2 release in J774 cells, a murine macrophage cell line. The role of endogenous NO in modulating TNF-α and IL-6 release was investigated using N-iminoethyl-L-ornithine (L-NIO), a specific inhibitor of NOS. L-NIO (10-1000...
The induction of cytokine expression in monocytes/macrophages by bacterial endotoxin or lipopolysaccharide is a critical, highly regulated host defence response. The augmentation of LPS responses by interferon gamma (IFN-γ), referred to as priming, is well established. However, the mechanism(s) by which priming occurs is poorly defined. Using tumour necrosis factor (TNF) induction as a model, experiments...
The current study was undertaken to investigate the role of TNF-R75 in regulation of E-selectin and ICAM-1 expression by TNF on HUVEC. To this end, we used agonistic anti-TNF-R75 antibodies, being mAb MR2-1 and polyclonal antibodies anti-TNF-R75 (pAb75). The agonistic properties of these antibodies were ascertained by the costimulatory capacity in a T-cell proliferation assay. These anti-TNF-R75 antibodies...
Mutagenesis of a region of human interleukin (IL)-6 which is important for triggering signal transduction via the IL-6 receptor β-chain (gp130) has lead to the isolation of a variant of human IL-6 (IL-6.Q160E/T163P), which could antagonize the biological activity of wild type IL-6 on the human EBV transformed B cell line CESS and the human hepatoma cell line HepG2. Surprisingly this antagonistic IL-6...
In order to study the role of platelets in inflammation we constructed a cDNA library from human platelet mRNA. By polymerase chain reaction (PCR) analysis of the library we have shown that platelets express mRNAs for the following chemokines: connective tissue activating peptide-III(CTAP-III), epithelial-derived neutrophil activating factor-78 (ENA-78), RANTES and monocyte chemotactic protein-3 (MCP-3)...
Administration of angiotensin-converting-enzyme (ACE) inhibitors reduce vascular proliferation following endothelial injury as well as progression of renal disease in various animal models. These effects might be due to interference with cytokines such as interleukin 1 (IL-1) or tumour necrosis factor α (TNF) since they have been implicated in regulating the effects of vascular cell growth factors...
The protein kinase C (PKC) inhibitors bisindolylmaleimide, calphostin C, H-7 and staurosporine were examined for their effect on tumour necrosis factor (TNF) cytotoxic activity. PKC inhibitors potentiated the cytotoxic activity of TNF in TNF-sensitive cell lines (CL8-1 melanoma and WEHI-164 fibrosarcoma), but had no effect on TNF cytolytic activity in TNF-resistant cells (BL6-8 melanoma and MCA-102...
Leukaemia Inhibitory Factor (LIF), an interleukin 6 (IL-6)-type cytokine, is an essential growth factor for murine embryonal stem cells. The LIF-receptor was known in these cells, but the cell-internal part of the signal cascade and the transcription factors through which LIF controls its growth-promoting target genes in embryonal stem cells, had not been identified. This study shows that the type...
The steady-state mRNA levels of the interleukin 6 receptor (IL-6R, gp80) and its signal transducing molecule, gp130, were examined in the rat hepatoma cell line, H-35, stimulated by cytokines IL-6, IL-1, oncostatin M (OSM) and/or Dexamethasone (Dex). In contrast to our previous findings in vivo [Geisterferet al., 1993,Cytokine, 5:1] in vitro Dex seemed to be the major stimulator of IL-6R mRNA expression,...
Neutralizing monoclonal antibodies against the murine interleukin 1 (IL-1) type I (mAb 35F5) and type II receptor (mAb 4E2) were used to passively immunize mice prior to exogenous murine IL-1α administration or a sterile-turpentine induced abscess. When mice were passively immunized with 35F5, the anorexia, weight loss and increased plasma acute phase protein levels in response to exogenous IL-1α...
Proinflammatory cytokines may stimulate replication and spread of HIV. To evaluate to what extent the female genital tract represents a source of these cytokines, we determined TNF-α, IL-1β and IL-6 concentrations in paired serum and cervicovaginal washings from 45 HIV-negative and 50 HIV-positive women, and then we looked for the relevant mRNAs in cervicovaginal secretions by RT-PCR. Cytokines were...
We investigated monocyte chemoattractant protein-1 (MCP-1) mRNA expression in rat vascular smooth muscle cells (VSMC) and in human atherosclerotic arteries to test the involvement of MCP-1 in the pathogenesis of atherosclerosis. In Northern blot analysis, MCP-1 mRNA expression was not observed in unstimulated cultured rat vascular smooth muscle cells (VSMC), but its expression was clearly observed...
The purpose of this study was to determine whether bacterial surface components other than lipopolysaccharide (LPS) could stimulate pro-inflammatory cytokine synthesis by mesenchymal and myelomonocytic cells in vitro. LPS, lipid A-associated proteins (LAP) and saline-extractable surface-associated material (SAM) were isolated from the periodontopathogenic bacteriumActinobacillus actinomycetemcomitansand...
We investigated whether cytokine genes were activated in human tumour-infiltrating mononuclear leukocytes (TIML) obtained from six lung adenocarcinomas and seven glioblastomas. TIML were extracted by mechanical disruption and isolated by double density gradient of Ficoll. We performed mRNA reverse transcription-polymerase chain reaction (RT-PCR) on these fresh (noncultured) TIML and autologous peripheral...
Genomic clones spanning the human type I and type II interleukin-1 receptor loci have been isolated. Approximately 75 kb of genomic DNA is required to encode the type I receptor, and approximately 38 kb to encode the type II receptor. In each case, the receptor coding region is contained in only about 20 kb of DNA, with most of the rest of each locus representing the distance between the two (type...
Malignant ascites of epithelial ovarian cancer patients contains high levels of interleukin 6 (IL-6). The present study was conducted to compare the secretion of IL-6 by seven different human ovarian cancer cell lines (OVCA) and cultured human peritoneal mesothelial cells (HPMC) and to examine the regulation of its production by other cytokines. IL-6 was detected in supernatant medium of all mesothelial...
Several cytokines have been identified as markers of early atherosclerotic disease during vascular injury and remodelling. Of particular importance, transforming growth factor-β(TGF-β1 ) has been found to be crucial in promoting connective tissue deposition resulting in both intimal and medial hyperplasia. However, the expression of TGF-β1 and β2 during cholesterol feeding in the Watanabe rabbit,...
Lymphocytes play an important part in the development and progression of a number of autoimmune and inflammatory disorders, which are characterized by the presence of activated T cells and cytokines at the site of tissue injury and in the circulation. There has been considerable interest in using dietary polyunsaturated fatty acids (PUFA), particularly then-3 PUFA found in fish oils, in the therapy...
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