Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614), a novel antiinflammatory compound, on the production of interleukin-1 (IL-1) and/or interleukin-6 (IL-6) by human monocytes and the THP-1 cells of a human monocytic cell line, were examined. T-614 inhibited the release of immunoreactive IL-1 beta from these cells stimulated with lipopolysaccharides (LPS) in a dose-dependent manner (0.3-30 micrograms/ml). The release of IL-6 from THP-1 cells, as determined by the assays for its hepatocyte-stimulating activities and immunoreactivities, was inhibited by T-614 with the IC50 values of 2.0 and 6.6 micrograms/ml, respectively. Northern blotting analysis using LPS-stimulated THP-1 cells indicated that the inhibitory effect of T-614 on IL-1 beta production is caused by the suppression of IL-1 beta mRNA expression. The inhibition of cytokine production by T-614 may provide an important insight into the additional mechanisms contributing to its antiinflammatory activities.
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PMID:Pharmacological studies on 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a novel antiinflammatory agent. 4th communication: inhibitory effect on the production of interleukin-1 and interleukin-6. 128

Although interferon-gamma has been shown to effectively prime macrophages for enhanced production of tumor necrosis factor-alpha (TNF alpha), it is reasonable to assume that other cytokines present in the extracellular environment may likewise facilitate cytokine biosynthesis. For example, interleukin-6 (IL-6) is synthesized by synovial lining macrophages and fibroblasts, and has been detected (along with TNF alpha) in rheumatoid synovial effusions. Therefore, the purpose of the present study was to determine whether IL-6 influences the production of IL-1 beta and/or TNF alpha by THP-1 macrophages. Although IL-6 treatment alone resulted in only a slight increase in TNF alpha levels, administration of IL-6 followed by Sal. minnesota LPS resulted in a synergistic potentiation of TNF alpha production by THP-1 macrophages. The priming effect of IL-6 could be reversed by boiling, or by the addition of a neutralizing polyclonal antibody against IL-6. Notably, IL-6 only weakly enhanced interleukin-1 beta production. In summary, the ability of IL-6 to potentiate TNF alpha production by THP-1 macrophages may provide insight into the regulation of the cytokine network in inflammatory diseases, such as rheumatoid arthritis.
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PMID:Interleukin-6 can prime THP-1 macrophages for enhanced production of tumor necrosis factor-alpha in response to LPS. 160 43

Human myelogenous leukemic cell lines (ML-1, U-937, THP-1) were induced to differentiate by treatment with various cytokines such as tumor necrosis factor (TNF), interferon-gamma (IFN-gamma) and interleukin-6. Serum of normal humans efficiently stimulated this cytokine-induced differentiation, whereas the stimulating effect of serum of brain tumor patients was much less. Both normal and patient sera, at effective concentrations, only slightly affected the binding of 125I-TNF to ML-1 cells, but any of these sera significantly inhibited the binding of 125I-IFN-gamma to U-937 cells or to THP-1 cells. These results suggest that the weak differentiation-stimulating effect of the serum of brain tumor patients cannot be explained simply by the modification of the binding of these cytokines to cellular receptors.
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PMID:Effect of sera of brain tumor patients on cytokine-induced human myelogenous leukemic cell differentiation. 185 Feb 19

Human myelogenous leukemic cell lines (ML-1, U-937, THP-1) were induced to differentiate by treatment with various cytokines such as tumor necrosis factor, interferon-gamma and interleukin-6. However, the extent of cell maturation depended upon the types and concentrations of sera included in the culture medium. The stimulating activity of human sera on the cytokine-induced differentiation significantly exceeded that of various lots of calf serum, horse serum, fetal calf serum and fetal bovine serum, and its stimulating effects were reproducibly observed irrespective of age and sex of normal volunteers. On Sephadex G-200 gel filtration chromatography, the stimulatory substance(s) present in human sera were separated from the inhibitory substance(s) eluted near the void volume.
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PMID:Dependence of cytokine-induced human myelogenous leukemic cell differentiation on the type of serum in the medium. 211 76

In the present report we compare the capacity of two related cytokines, tumor necrosis factor (TNF) alpha and lymphotoxin (LT), to modulate mRNA levels of interleukin-6 (IL-6) in cells representing different stages of monocytic differentiation including the human leukemia cell lines HL 60, U 937, THP-1, MonoMac 1 and peripheral blood monocytes. We show that the capacity of TNF alpha and LT to induce IL-6 mRNA accumulation increases as monocytic differentiation proceeds with TNF alpha being more potent than LT, suggesting that alternate pathways may be used by differentiating cells to control expression of IL-6. In contrast, in monocytes which constitutively synthesize IL-6 transcripts, TNF alpha and LT treatment had opposite effects on levels of IL-6 mRNA accumulation. In these cells TNF alpha enhanced steady state levels of IL-6 transcripts due to mRNA stabilization, whereas LT shortened IL-6 mRNA half-life, most likely due to induction of a RNA destabilizer since LT-mediated downregulation of levels of IL-6 mRNA in monocytes could be prevented by inhibition of protein synthesis. Neither TNF alpha nor LT altered IL-6 mRNA accumulation by interfering with preexisting transcription factors since both TNF alpha and LT required de novo protein synthesis to exert their effects.
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PMID:Mechanisms of differential regulation of interleukin-6 mRNA accumulation by tumor necrosis factor alpha and lymphotoxin during monocytic differentiation. 968 34

We investigated the molecular basis of the synergistic induction by interferon-gamma (IFN-gamma)/tumor necrosis factor-alpha (TNF-alpha) of human interleukin-6 (IL-6) gene in THP-1 monocytic cells, and compared it with the basis of this induction by lipopolysaccharide (LPS). Functional studies with IL-6 promoter demonstrated that three regions are the targets of the IFN-gamma and/or TNF-alpha action, whereas only one of these regions seemed to be implicated in LPS activation. The three regions concerned are: 1) a region between -73 and -36, which is the minimal element inducible by LPS or TNF-alpha; 2) an element located between -181 and -73, which appeared to regulate the response to IFN-gamma and TNF-alpha negatively; and 3) a distal element upstream of -224, which was inducible by IFN-gamma alone. LPS signaling was found to involve NF kappa B activation by the p50/p65 heterodimers. Synergistic induction of the IL-6 gene by IFN-gamma and TNF-alpha, in monocytic cells, involved cooperation between the IRF-1 and NF kappa B p65 homodimers with concomitant removal of the negative effect of the retinoblastoma control element present in the IL-6 promoter. This removal occurred by activation of the constitutive Sp1 factor, whose increased binding activity and phosphorylation were mediated by IFN-gamma.
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PMID:Triggering of the human interleukin-6 gene by interferon-gamma and tumor necrosis factor-alpha in monocytic cells involves cooperation between interferon regulatory factor-1, NF kappa B, and Sp1 transcription factors. 749 67

The supernatant of a cell line of squamous cell carcinoma of the head and neck (SCCHN), PCI-50, was previously shown to induce activation, promote proliferation and increase antitumor cytotoxicity of freshly purified human natural killer (NK) cells and CD4+ T lymphocytes [Arch Otolaryngol Head Neck Surg (1994) in press]. This supernatant was found also to promote the growth of a variety of hematopoietic cell lines, including Jurkat, THP-1, K562, NK-92 or Epstein-Barr-virus-transformed B cell lines. The Jurkat cell line was selected as a reporter cell in an 18-h proliferation assay established to measure the growth-promoting activity of PCI-50 supernatant. The presence of soluble tumor-derived factors able to induce proliferation of Jurkat cells was demonstrated in the supernatant produced by several other SCCHN cell lines but not in that produced by a gastric cancer cell line (HR) or renal cell carcinoma line (5117G8). The growth-promoting PCI-50 supernatant was shown to contain 28 +/- 0.5 pg/ml interleukin-6 (IL-6) in vitro but was negative for interferon gamma, IL-1, IL-2, IL-4, tumor necrosis factor alpha, granulocyte/macrophage-colony-stimulating factor and IL-12. The addition of any of these recombinant cytokines to Jurkat cell cultures did not significantly promote growth, while PCI-50 supernatant was consistently growth-stimulatory. This supernatant neither enhanced intracellular Ca2+ concentration in Jurkat cells nor induced up-regulation of activation antigens on the cell surface, although it supported growth of Jurkat cells in the absence of IL-2. The growth-promoting activity in the PCI-50 supernatant was acid-labile at pH 2 for 4 h, heat-resistant at 96 degrees C for 1 h and sensitive to treatments with trypsin and pepsin. Preincubation of the PCI-50 producer cells with tunicamycin or cyclohexamide reduced the level of growth-promoting activity in the supernatant. A partial purification of this activity was achieved using Amicon filtration, chromatography on concanavalin-A-Sepharose and then a hydroxyapatite column and high-pressure liquid chromatography gel filtration. The partially purified glycoprotein had a molecular mass of 50-70 kDa, as determined by gel filtration.
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PMID:Proliferation of hematopoietic cell lines induced by a soluble factor derived from human squamous cell carcinomas of the head and neck. 800 Oct 29

Serum amyloid A (apoSAA) is a family of proteins found, mainly associated with high density lipoproteins, in the blood plasma of mammals and at least one avian species, the Pekin duck. These proteins are present in small amounts under normal circumstances, but their concentration is capable of rising 100- to 1,000-fold in situations involving tissue injury or infection. Like classic acute phase proteins they are produced in the liver; however, expression of one of the apoSAA genes is known to occur in activated macrophages of mice. We examined three human macrophage precursor cell lines (THP-1, U-937, and HL-60), before and after differentiation with phorbol 12-myristate 13-acetate or 1 alpha,25-dihydroxy-vitamin D3, for apoSAA messenger (m)-RNA expression and found that: 1) induction of steady-state apoSAA mRNA by lipopolysaccharide, interleukin-1, or interleukin-6 required the presence of the synthetic glucocorticoid dexamethasone; 2) the three known active genes, apoSAA1, apoSAA2, and apoSAA4, were induced in THP-1 cells, whereas the pseudogene apoSAA3 was not; 3) differentiated and undifferentiated THP-1 cells expressed apoSAA mRNA, but U-937 cells expressed apoSAA mRNA (low levels) only after phorbol 12-myristate 13-acetate differentiation and HL-60 cells did not express apoSAA mRNA whether differentiated or not; 4) apoSAA protein was detectable immunologically at a low level in lyophilized medium from induced THP-1 cells. Our findings are compatible with the hypotheses that 1) apoSAA gene expression in human monocytes/macrophages in vivo is differentiation dependent; 2) activated macrophages provide a local source of apoSAA at sites of tissue injury or inflammation; 3) apoSAA is induced in tissue macrophages by local stimuli, under conditions that may not evoke the systemic acute phase response.
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PMID:Human serum amyloid A genes are expressed in monocyte/macrophage cell lines. 808 47

We have previously observed that delta 9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, increased supernatant interleukin-1 (IL-1) bioactivity in cultures of mouse resident peritoneal macrophages stimulated with lipopolysaccharide (LPS). In this study, experiments were performed to determine whether THC treatment similarly affected phagocytes of human origin. The results showed that THC increased the levels of supernatant IL-1 bioactivity of two human monocytic cell lines, but only if the cells were differentiated with phorbol myristate acetate. Undifferentiated cells displayed decreased IL-1 bioactivity in response to THC. However, under conditions in which THC augmented supernatant IL-1 bioactivity from THP-1 cells, ELISA studies showed that the levels of IL-1 alpha and IL-1 beta were unchanged and decreased, respectively. Furthermore, supernatant interleukin-6 (IL-6) levels were decreased, but tumor necrosis factor (TNF-alpha) levels were increased by THC treatment. These results show that THC treatment modulates cytokine production and/or release by mouse and human macrophages and the drug effects on IL-1-like bioactivity in the supernatants of the human THP-1 cells are due to increased levels of other cytokines, such as TNF-alpha, rather than IL-1 itself.
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PMID:delta 9-Tetrahydrocannabinol (THC) modulates IL-1 bioactivity in human monocyte/macrophage cell lines. 816 9

Manifestations of HIV-1 infection such as fever, hypergammaglobulinemia, and interstitial pneumonitis may be due to increased production of inflammatory cytokines such as interleukin-1 and interleukin-6 (IL-6). Monocytes/macrophages of HIV-1-infected individuals have been noted to produce increased amounts of IL-6, as well as to have enhanced accessory cell function. These studies examined the ability of HIV-1 tat, an important HIV-1 regulatory gene, to modulate monocyte/macrophage function. In these experiments, HIV-1 tat-transfected THP-1 cells, a monocytic cell line, enhanced THP-1 immune accessory cell function in the presence of pokeweed mitogen and concanavalin A. HIV-1 tat-transfected cells also increased production of lipopolysaccharide-stimulated IL-6 mRNA and IL-6 protein. The ability of monocytes/macrophages to support HIV-1 production while exhibiting little or no cytopathic effects allows these cells to serve as a reservoir for the virus. The ability of HIV-1 tat to regulate cellular function in monocytes/macrophages may play an important part in the pathogenesis of HIV-1 infection.
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PMID:Modulation of accessory cell function and interleukin-6 production by the HIV-1 tat gene. 817 23


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