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The production of interleukin 6 (IL-6) was studied in human gingival fibroblasts challenged with bradykinin (BK), in the presence or absence of either tumour necrosis factor α (TNF-α) or interleukin 1 (IL-1). The inflammatory mediator BK as well as the cytokine TNF-α and IL-1β dose dependently stimulated IL-6 production in gingival fibroblasts. When the cells were treated simultaneously with BK and...
Peptidases play an important role in the regulation of peptide-mediated effects. Modulation of peptidase activity may therefore be a major mechanism to control peptide actions. Our aim was to analyse the effects of cytokine and glucocortoids on peptidases expressed by human bronchial epithelial cells, which have been shown to be an important site for peptidase activity.The effects of cytokines [interleukin...
Interleukin 3 (IL-3) and stem cell factor (SCF) are both important regulators of early haemopoietic cell development. Here, we have compared their effects on the kinetics of erythroid burst formation by BFU-E in normal adult bone marrow. We grew the BFU-E in the presence of erythropoietin (Epo) alone, Epo+IL-3 or Epo+SCF and scored the numbers of subcolonies in individual bursts after 14 days. The...
Interleukin 8 (IL-8) is a member of the CXC subfamily of chemokines which attracts and activates preferentially neutrophilic granulocytes. At nanomolar concentrations monomeric and dimeric forms of the molecule are in equilibrium, with the monomer being the prevalent form. Five amino acids from position 23 to 29 of the 72-amino acid IL-8 sequence form the dimer interface, with Leu25 and Val27 being...
Metformin reduces insulin resistance and hyperinsulinaemia, as well as lipid levels and body weight. The mechanisms behind these effects are likely to involve intracellular insulin signalling. Recent evidence implicates tumour necrosis factor α (TNF-α) as a modulatory factor on insulin resistance. The present investigation was undertaken to clarify whether metformin affects TNF-α and soluble TNF receptor...
Interleukin 6 (IL-6) and related gp130-signalling cytokines rapidly activate latent cytoplasmic Stat transcription factors and these are believed to play pivotal roles in the expression of downstream cytokine-responsive genes. We have previously shown in IL-6 deficient ( −/− ) mice that IL-6 is absolutely required for the transcriptional induction of acute phase response (APR) genes in the...
The regulation of macrophage lipoprotein lipase (LPL) by cytokines is of potentially crucial importance in the pathogenesis of atherosclerosis. The effect of combinations of interleukin-1 (IL-1), -6 (IL-6), and -11 (IL-11), interferon gamma (IFN-γ), leukaemia inhibitory factor (LIF) and tumour necrosis factor alpha (TNF-α) on the expression of LPL in macrophages was studied using the murine J774.2...
The infection of human peripheral blood leukocytes (hPBL) with Sendai virus in vitro, induces the synthesis of human leukocyte interferons (IFN-αn3) as well as other cytokines. The authors discovered that supernatants of virus-infected hPBL also contained significant amounts of platelet-derived growth factor AB (PDGF-AB). The concentrations of immunogenic PDGF-AB in the interferon batches were determined...
Cardiotrophin-1 (CT-1), a newly discovered cytokine, has been shown to induce cardiac hypertrophy in vitro and in vivo. The present study examined the effects of CT-1 on haemodynamics and cardiac function. The measurements of haemodynamic parameters were made using in-dwelling catheters and flow probes in conscious, unrestrained rats. Intravenous administration of CT-1 caused a dose-dependent decrease...
Macrophage colony-stimulating factor (M-CSF), initially described as a growth factor of the mononuclear phagocytic lineage, also participates in immunological and inflammatory reactions, bone metabolism and pregnancy. All its biological activities are mediated by a tyrosine kinase receptor (M-CSF-R) that is encoded by the c-fmsprotooncogene. After a brief overview on the synthesis, structure, metabolism...
The authors have previously shown that 26-kDa membrane-bound tumour necrosis factor precursor (proTNF) on the cell-surface of primed human monocytic cell line THP-1 is involved in positive feedback regulation of lipopolysaccharide (LPS)-dependent TNF-production. Here, we provide direct evidence for modulation of responsiveness of the THP-1 cells against LPS by membrane-bound proTNF. When THP-1 cells...
Fifty-five adult patients with primary bone tumour, 27 benign and 28 malignant tumours, were assayed for leukaemia inhibitory factor (LIF) in urine and serum samples. Supernatant was obtained from primary tumour tissue cultures in 24 cases (14 benign, 10 malignant tumours). LIF was found in 11 urine samples (16.7%, 1 benign and 10 malignant tumours). In 23 urine samples from patients with malignant...
By using a specific enzyme-linked immunosorbent assay, the authors demonstrated that human bone marrow stromal cells produce IL-6 and IL-8. Their synthesis is enhanced in a dose-dependent manner after stimulation with lipopolysaccharide (LPS) and phorbol myristate acetate (PMA). Interleukin 6 (IL-6) and IL-8 production in response to PMA were markedly diminished by the PKC inhibitor staurosporine...
Though oncostatin M (OSM) is a potent mediator of the inflammatory reaction, its role in inflammation and bone resorption is still unclear. A long-term bone-marrow culture system is usually developed to allow the formation of multinucleated cells (MNC) and was used here to define the effects of human recombinant OSM on human MNC formation. OSM significantly upregulated (1.9- to 5.6-fold) the number...
Interleukin 12 (IL-12) plays a crucial role in defensive immune responses, modulation of cytokine production and is involved in the pathogenesis of some autoimmune diseases. The authors investigated whether decreased in vitro production of IL-12 occurs in systemic lupus erythematosus (SLE), in which the cytokine secreting pattern is predominantly type 2. IL-12 production by SLE peripheral blood mononuclear...
Mice injected with lipopolysaccharide (LPS) develop lethal septic shock, accompanied by elevated serum NO x , interferon γ (IFN-γ), tumour necrosis factor α (TNF-α) and TNF-receptor levels. Elevated NO levels are thought to play a central role in tissue damage observed during septic shock. In vitro data indicate that IFN-γ and TNF-α play an important role in LPS-induced NO release. Further,...
Interleukin 12 (IL-12) is a key cytokine in regulating type 1 or type 2 cytokine production and in determining the nature of immune responses. Our previous studies demonstrated that its production was significantly impaired in systemic lupus erythematosus (SLE) patients and this deficient IL-12 production was mainly mediated by excessive endogenous IL-10. The present study was designed to further...
The toxicity of high-dose interleukin 2 (IL-2) treatments limits its use in tumour therapies, particularly in older age groups, characterized by a reduced tolerance to antineoplastic therapies. Here, we evaluated the possibility to induce cytotoxic lymphokine-activated killer (LAK) cells through a brief exposure (1-h pulse) of peripheral blood mononuclear cells (PBMC) from elderly cancer patients...
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