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)

Conventional lactate (Lac)-buffered peritoneal dialysis (PD) solutions have turned out to be detrimental to human peritoneal cells, especially because of a low pH. In the present study, we focus on potential differences between Lac and bicarbonate (Bic) as a buffer when adjusted to a physiological pH. All test fluids were buffered with either 40 mmol/L of Lac or 34 mmol/L of Bic, sterile filtered, and adjusted to a pH of 7.4. Osmotic agents used were 1.36% glucose (Glu), 3.86% Glu, 1% amino acids (AA), and 7.5% Glu polymer (Glupoly). Human peritoneal mesothelial cells (HPMCs) were isolated from the omentum majus, grown to confluence, and incubated after the second passage for 15 minutes (37 degrees C and 5% carbon dioxide) with the test fluids. Cytotoxicity was controlled by measuring apoptotic and necrotic cells with cytofluorometry. Aerobic cell metabolism (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assay) and intracellular adenosine triphosphate (ATP) concentrations were measured to assess cell viability. Release of interleukin-6 (IL-6) from HPMCs was determined as a parameter of cellular host defense. No significant difference in apoptosis or necrosis rates was found between the solutions adjusted to normal pH. However, in the MTT assay, Bic solutions were superior to corresponding Lac pendants at an identical pH of 7.4 (P < 0.01). Intracellular ATP concentrations reflected a very similar pattern (P < 0.05). Glupoly in combination with Lac showed an impaired pattern with both the MTT and ATP assays. Regarding IL-1beta-stimulated IL-6 release, there was a small, but not significantly better, response for Bic. Differences in manifest cell cytotoxicity reflected by apoptosis and necrosis rates could not be detected comparing PD solutions buffered with Lac or Bic at a physiological pH. However, distinct parameters of cell metabolism were superior with Bic compared with Lac. Especially Glupoly was inferior in combination with Lac as a buffer.
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PMID:Peritoneal dialysis fluids with a physiologic pH based on either lactate or bicarbonate buffer-effects on human mesothelial cells. 1157 93

We evaluated the use of recombinant human interleukin-6 (rhIL-6) and a monoclonal antibody specific for interferon-gamma (IFN-gamma) as co-adjuvants in a subunit vaccine against tuberculosis consisting of the culture filtrate proteins of Mycobacterium tuberculosis (ST-CF) emulsified in the adjuvant dimethyl-dioctadecylammonium bromide (DDA). Both the addition of rhIL-6 and the neutralization of IFN-gamma resulted in an increased T helper type 1 (Th1) response characterized by enhanced IFN-gamma production and cell proliferation. Nevertheless, this did not result in the enhancement of protection against either an intravenous or an aerosol M. tuberculosis challenge. Our data stress the need to identify further correlates of protection in addition to IFN-gamma production to screen vaccines against tuberculosis infection.
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PMID:Failure to induce enhanced protection against tuberculosis by increasing T-cell-dependent interferon-gamma generation. 1168 55

1. We examined the effects of endogenous prostaglandin E(2) (PGE(2)) on the production of interleukin-6 (IL-6), macrophage colony stimulating factor (M-CSF), and vascular endothelial growth factor (VEGF) by interleukin-1beta (IL-1beta)-stimulated human synovial fibroblasts. 2. NS-398 (1 microM), a cyclo-oxygenase-2 (COX-2) inhibitor, inhibited IL-6 and VEGF production (35+/-4% and 26+/-2%, respectively) but enhanced M-CSF production (38+/-4%) by IL-1beta (1 ng ml(-1)) in synovial fibroblasts isolated from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Exogenous PGE(2) completely abolished the effects of NS-398 on the production of each mediator by OA fibroblasts stimulated with IL-1beta. 3. 8-Bromo cyclic AMP and dibutyryl cyclic AMP, cyclic AMP analogues, mimicked the effects of PGE(2) on IL-6, M-CSF, and VEGF production by OA fibroblasts. 4. The EP(2) selective receptor agonist ONO-AE1-259 (2 nM) and the EP(4) selective receptor agonist ONO-AE1-329 (2 or 20 nM), but not the EP(1) selective receptor agonist ONO-DI-004 (1 microM) and the EP(3) selective receptor agonist ONO-AE-248 (1 microM), replaced the effects of PGE(2) on IL-6, M-CSF, and VEGF production by OA and RA fibroblasts stimulated with IL-1beta in the presence of NS-398. 5. Both OA and RA fibroblasts expressed mRNA encoding EP(2) and EP(4) but not EP(1) receptors. In addition, up-regulation of EP(2) and EP(4) receptor mRNAs was observed at 3 h after IL-1beta treatment. 6. These results suggest that endogenous PGE(2) regulates the production of IL-6, M-CSF, and VEGF by IL-1beta-stimulated human synovial fibroblasts through the activation of EP(2) and EP(4) receptors with increase in cyclic AMP.
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PMID:Regulation by PGE2 of the production of interleukin-6, macrophage colony stimulating factor, and vascular endothelial growth factor in human synovial fibroblasts. 1201 Jul 78

Oxidative stress plays an important role in neuronal cell death associated with many different neurodegenerative conditions, and it is reported that 4-hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation, is a key mediator of neuronal cell death induced by oxidative stress. Previously, we have demonstrated that interleukin-6 (IL-6) protects PC12 cells from serum deprivation and 6-hydroxydopamine-induced toxicity. Therefore, in the present study, we examined the effects of interleukins on HNE toxicity in PC12 cells. Exposure of PC12 cells to HNE resulted in a decrease in levels of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, which was due to necrotic and apoptotic cell death. Addition of IL-6 24 h before HNE treatment provided a concentration-dependent protection against HNE toxicity, whereas neither IL-1beta nor IL-2 had any effect. Addition of glutathione (GSH)-ethyl ester, but not superoxide dismutase or catalase, before HNE treatment to the culture medium protected PC12 cells from HNE toxicity. We found that IL-6 increases intracellular GSH levels and the activity of gamma-glutamylcysteine synthetase (gamma-GCS) in PC12 cells. Buthionine sulfoximine (BSO), an inhibitor of gamma-GCS, reversed the protective effect of IL-6 against HNE toxicity. These results suggest that IL-6 protects PC12 cells from HNE-induced cytotoxicity by increasing intracellular levels of GSH.
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PMID:Interleukin-6 protects PC12 cells from 4-hydroxynonenal-induced cytotoxicity by increasing intracellular glutathione levels. 1205 70

Incidence rates of ovarian cancer remain lowest in Asian nations, which consume diets rich in soy products, whereas they remain among the highest in the United States and other Western nations, which consume low amounts of soy foods. The hypothesis of this study is that soy-derived isoflavones inhibit the proliferation of ovarian cancer cells in vitro by regulating cytokine synthesis. Cell proliferation was evaluated by bromodeoxyuridine and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA synthesis of Caov-3 and NIH:OVCAR-3, two ovarian cancer cell lines, was significantly inhibited by genistein or daidzein at dietarily relevant concentrations (10(-8)-10(-10) M). Also, the number of viable cells was significantly lower (45-75%) in all isoflavone-treated groups than in the control group (P < 0.01). The addition of ICI-182780, an estrogen antagonist, blocked these inhibitory effects. In addition, interleukin-6 synthesis by these two cell lines was inhibited by genistein or daidzein; production was decreased by approximately 20% compared with the control group (P < 0.05). In contrast, transforming growth factor-beta 1 production in ovarian cancer cells incubated with genistein or daidzein was significantly greater, i.e., by approximately 30%, than in the control group (P < 0.05). Addition of ICI-182780 also neutralized the effects of isoflavones on the production of these two cytokines by ovarian cancer cells. In summary, genistein and daidzein independently modify cytokine production and reduce ovarian cancer cell proliferation via, at least in part, an estrogen receptor-dependent pathway.
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PMID:Isoflavones inhibit proliferation of ovarian cancer cells in vitro via an estrogen receptor-dependent pathway. 1209 20

The objective of this study was to investigate the ability of alendronate and taurine in inhibiting in vitro osteoclast differentiation induced by bacteria. Whole cell sonicates of Porphyromonas gingivalis were used as an osteoclast-stimulating factor in a mouse coculture system and differentiated osteoclasts were confirmed by tartrate-resistant acid phosphatase (TRAP) staining. Alendronate at the concentrations of 10(-7) M, 10(-6) M, and 10(-5) M and taurine at the concentrations of 4 mM, 8 mM, and 12 mM were used. The cytotoxic effects of alendronate and taurine were examined using methylthiazole-tetrazolium bromide (MTT) assay. The amounts of interleukin-6 (IL-6) in culture supernatants were also measured using ELISA. The sonicates of P. gingivalis at the concentration of 0.01-0.1 microg/ml significantly stimulated the formation of osteoclasts (p < 0.05). Alendronate (10(-5) M) and taurine (12 mM) significantly suppressed the sonicate-stimulated osteoclast formation. In MTT assay, no cytotoxic effects were evident in all concentrations of alendronate and taurine. Alendronate and taurine did not affect the amount of IL-6 induced by P. gingivalis sonicates. These data indicate that alendronate and taurine have inhibitory effects on bacteria-stimulated osteoclast formation in vitro and that this inhibitory mechanism is not related to the blocking of IL-6 production.
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PMID:The inhibitory effect of alendronate and taurine on osteoclast differentiation mediated by Porphyromonas gingivalis sonicates in vitro. 1254 Feb 15

Inhalation of organic dust from a swine-confinement building leads to an intense inflammatory reaction with an increased number of inflammatory cells and mediators in the upper and lower respiratory tract of previously unexposed subjects. In vitro the dust induces cytokine release from epithelial cells and alveolar macrophages. It is known that intracellular cyclic AMP (cAMP) contributes to the regulation of inflammatory responses. We therefore investigated whether 8-Bromo-cAMP, a cell membrane-permeable cAMP analogue, would influence release of the cytokines interleukin-6 (IL-6) and IL-8 in a human airway epithelial cell line, A549, exposed to a suspension of the organic dust, and to a supernatant prepared by centrifugation (at low g-force) of a suspension of dust. The large particulate matter was thus sedimented, leaving bacteria, whole and cell wall constituents in the supernatant. Cytokine release was measured with enzyme-linked immunosorbent assay (ELISA). The cytokine release induced by a supernatant was 23% (IL-6) and 27% (IL-8) of the release induced by a dust suspension. 8-Bromo-cAMP (1 mM) doubled basal IL-6 release and IL-6 release induced by a dust supernatant (P<0.01), and increased IL-6 release induced by a dust suspension by 19% (P<0.05). 8-Bromo-cAMP did not affect basal IL-8 release, partially inhibited (28%) the release of IL-8 induced by a dust suspension (P<0.01), but increased IL-8 release induced by a dust supernatant by 13% (P<0.05). In summary, expression of the cytokines IL-6 and IL-8 is differentially regulated by 8-Bromo-cAMP, both with regard to basal and dust-induced release. The results indicate that 8-Bromo-cAMP attenuated IL-8 release by affecting signaling transductions induced by the particulate fraction.
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PMID:Effects by 8-bromo-cyclicAMP on basal and organic dust-induced release of interleukin-6 and interleukin-8 in A549 human airway epithelial cells. 1255 10

In the present study we investigated the role of platelet-activating factor (PAF) and interleukin-6 (IL-6) in delaying polymorphonuclear neutrophil (PMN) apoptosis. Isolation of PMN was performed by using the discontinuous plasma-Percoll gradient technique. PMN was cultured in enriched RPMI 1640 media at 2 x 10(7) PMN/ml for 24 h. Subgroups were treated with IL-6 or PAF or pretreated with PAF receptor antagonist BN52021 before IL-6 or PAF were added. Morphological assessment and quantitation of apoptosis were performed with acrodine/ethidium bromide stain and epifluorescent microscope. The results showed that both IL-6 and PAF suppressed PMN apoptosis. Pretreatment of PMN with BN52021 abrogated the effects of IL-6 and PAF. It is suggested that PAF may be a crucial cytokine in the suppression of PMN apoptosis. These observations may contribute to elucidating the mechanisms of IL-6 and PAF in mediating postinjury hyperinflammation and secondary organ dysfunction and provide a clue for the prevention and treatment of the conditions.
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PMID:[Role of interleukin-6 and platelet-activating factor in delaying neutrophil apoptosis]. 1272 51

Recent evidence suggests that CD38, an ectoenzyme that converts NAD(+) to cyclic ADP-ribose (cADPr), may play a role in cytokine-induced airway smooth muscle (ASM) cell hyper-responsiveness, a key feature associated with chronic asthma. In the present study, we investigated the major signaling pathways by which tumor necrosis factor-alpha (TNFalpha) induces CD38 expression and its role in regulating gene expression in human ASM cells. Using flow cytometry analyses, TNFalpha enhanced CD38 expression in a manner that was time-(0-24 h), concentration-(0.1-40 ng/ml), and protein synthesis-(cycloheximide blockade) dependent. A selective agonistic antibody against tumor necrosis factor receptor (TNFR) 1 also augmented CD38 expression, whereas anti-TNFR2 antagonistic antibody did not prevent the TNFalpha response. Inhibition of the Janus activated kinase/signal transducer and activator of transcription pathways using the soluble inhibitor 2-(1,1-dimethylethyl)-9-fluoro-3,6-dihydro-7H-benz-[h]imidaz[4,5-f]isoquinolin-7-one (DBI) or with neutralizing antibody against interferon beta (IFNbeta) completely abrogated TNFalpha-induced CD38 expression at both protein and mRNA levels. Combining TNFalpha (0.1 and 1 ng/ml) and IFNbeta (100 IU/ml) at concentrations alone that had little effect on CD38 expression induced a robust synergistic induction of CD38 mRNA and protein levels. 8-Bromo-cADPr, a cADPr antagonist, significantly augmented TNFalpha-induced interleukin-6 secretion, whereas regulated on activation normal T cell expressed and secreted secretion was suppressed. 8-Bromo-cADPr, however, did not affect TNFalpha-induced cell surface expression of intercellular adhesion molecule-1. Our study is the first to demonstrate that IFNbeta-dependent activation of CD38 pathway is a novel component by which TNFalpha differentially regulates the expression of inflammatory genes in ASM cells.
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PMID:Tumor necrosis factor-alpha differentially regulates the expression of proinflammatory genes in human airway smooth muscle cells by activation of interferon-beta-dependent CD38 pathway. 1526 23

Interleukin-6 (IL-6) has been shown to regulate both growth and neuroendocrine (NE) differentiation in some types of human cancer cells, and erbB2 may be a critical component of IL-6 signaling. Non-small cell lung cancer (NSCLC) tumors that demonstrate NE properties have been suggested to have biological characteristics similar to small cell lung cancers with initial responsiveness to chemotherapy. We investigated whether IL-6 is implicated in the cell growth, NE differentiation, and chemosensitivity of NSCLC-NE cells. NSCLC-NE cells were treated with exogenous IL-6, and a subclone of an IL-6-transfected NSCLC cell line that constitutively expressed IL-6 receptor was also generated. These cells were assessed for cell proliferation by cell counting and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays, chemosensitivity to cisplatin and etoposide by MTT assays, and NE differentiation by observing morphological changes and immunoblotting for neuron-specific enolase (NSE). The IL-6-treated cells and the IL-6-transfected cells showed enhanced cell proliferation and downregulated NSE expression, but little change in chemosensitivity. In the culture medium, IL-6-transfected cells grew as looser aggregates than the parental cells. IL-6 could not activate the erbB genes. In conclusion, IL-6 can induce cell proliferation and NE dedifferentiation but has little effect on chemosensitivity in IL-6 receptor-expressing NSCLC-NE cells. The status of NSE expression is unlikely to be a crucial factor for chemosensitivity in NSCLC cells.
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PMID:Role of IL-6 in neuroendocrine differentiation and chemosensitivity of non-small cell lung cancer. 1589 59


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