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)

Metabolic syndrome is associated to chronic low grade inflammation, characterized by increased levels of inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-6 (IL-6). In particular, TNF-alpha causes a decrease in the insulin-stimulated kinases related to the early phases of the insulin cascade, thereby leading to insulin resistance. Etanercept is a human fusion protein used in the treatment of psoriasis and inflammatory arthritis. It blocks inflammatory response by interfering in the binding of TNF-alpha to its receptors. The aim of this case report study is to verify the effect of Etanercept on insulin sensitivity, lipid profile and inflammatory status in psoriatic patients. Nine psoriatic patients with stable, active, plaque type psoriasis were enrolled and treated with Etanercept for 24 weeks. We found an improvement in the metabolic assessment with a significant reduction of insulin plasma levels. In particular, this treatment allows to maintain their euglycemic state with lower insulin plasma levels, as confirmed by the improved Homeostasis Model Assessment (HOMA) index. We conclude that Etanercept, probably acting on inflammation, improves insulin sensitivity in psoriatic subjects.
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PMID:Effect of etanercept on insulin sensitivity in nine patients with psoriasis. 1817 45

Adipose tissue secretions play an important role in the development of obesity-related pathologies such as diabetes. Through inflammatory cytokines production, adipose tissue stromavascular fraction cells (SVF), and essentially macrophages, promote adipocyte insulin resistance by a paracrine way. Since xanthine family compounds such as caffeine were shown to decrease inflammatory production by human blood cells, we investigated the possible effect of caffeine on Tumor Necrosis Factor alpha (TNFalpha) and Interleukin-6 (IL-6) expression by human adipose tissue primary culture. For that purpose, human subcutaneous adipose tissue obtained from healthy non-obese women (BMI: 26.7 +/- 2.2 kg/m2) after abdominal dermolipectomy, was split into explants and cultured for 6 hours with or without caffeine. Three different concentrations of caffeine were tested (0.5 microg/mL, 5 microg/mL and 50 microg/mL). After 6 hours of treatment, explants were subjected to collagenase digestion in order to isolate adipocytes and SVF cells. Then, TNFalpha and IL-6 mRNA were analysed by real-time PCR alternatively in adipocytes and SVF cells. In parallel, we checked gene expression of markers involved in adipocyte differenciation and in SVF cells inflammation and proliferation. Our findings show a strong and dose dependent down-regulation of TNF-alpha gene expression in both adipocyte and SVF cells whereas IL-6 was only down regulated in SVF cells. No effect of caffeine was noticed on the other genes studied. Thus, caffeine, by decreasing TNFalpha expression, could improve adipose tissue inflammation during obesity.
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PMID:Caffeine reduces TNFalpha up-regulation in human adipose tissue primary culture. 1845 8

Developing biocompatible polymeric platforms for drug delivery with enhanced localized activity represents a key facet of advanced interventional therapy. In this work, the drug-eluting potential of an amine-functionalized poly- p-xylene commonly known as Parylene A (4-amino(2,2)paracyclophane) was conducted with the microfilm device consisting of a primary base layer, drug film, and a secondary eluting layer presenting exposed amine groups which enhance the range of modifications that can be incorporated into the film. The murine macrophage cell line RAW 264.7 served as a cellular response to dexamethasone, a synthetic anti-inflammatory glucocorticoid and doxorubicin, an anticancer therapeutic. Decreased expression of NFkappa-B-mediated cytokines Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNFalpha), resultant DNA fragmentation, and spectroscopic analysis revealed the efficient and localized drug-eluting properties of the Parylene A polymeric bilayer.
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PMID:Localized therapeutic release via an amine-functionalized poly-p-xylene microfilm device. 1871 31

Immune modulating activity of ethanol extracts from Glycyrrhiza uralensis Fisch was investigated by conserving growth characteristics of several human cell lines. All of the samples did not show severe cytotoxicity on normal human liver cell line, WRL-68, showing less than 25% inhibition of cell growth. The crude extract and its fractionized samples (F1 and F3) inhibited the growth of human hepatoma, Hep3B, down to ca. 70% of normal cell growth in adding 1.0 g l(-1) of fraction F3. The result of anticancer experiments was well matched to the results of antimutagenicity using Chinese Hamster Lung cell lines(CHL V79). In adding 1.0 g l(-1) of fraction F1, the growth of human B cell was enhanced, up to 60% of control growth. The secretion of two kinds of cytokines, Interleukin-6 and Tumor Necrosis Factor-alpha from human B cells was also enhanced in adding the crude extract, but not the standards such as Glycyrrhizin (GL) or 18,beta-glycyrrhetinic acid (GM). It was found that both of the apoptosis and differentiation were more accelerated in supplementing the crude extract and fraction F1 than in adding the standards. A spot was found only in the crude extract and fractions, not standards by Thin Layer Chromatography(TLC) analysis. It tells that there must be another unknown component in crude and/or fraction F1 as a possible candidate of immune modulators. This component seems to be a derivative of a monomer, GM since its R(f) was close to the monomer. It was also interesting that glycyrrhizin, a major component in G. uralensis Fisch was biologically activated by first being hydrolyzed by an enzyme.
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PMID:Effect of the extracts from Glycyrrhiza uralensis Fisch on the growth characteristics of human cell lines: Anti-tumor and immune activation activities. 1900 15

Low-grade inflammatory responses may be related to the pathogenesis of cancer-related fatigue (CRF). We investigated circulating levels of various inflammatory markers in relation to chronic CRF (6 month duration) in Norwegian long-term survivors of testicular cancer (TCSs). We compared 92 TCSs with chronic CRF (cases) to 191 TCS without (controls) at median age 45 years (range 23-73), and median 11 years post-treatment (range 5-20). Chronic CRF was defined using the Fatigue Questionnaire, while plasma concentrations of cytokines and serum CRP were determined by various immunoassays. Higher levels of interleukin-1 receptor antagonist (IL-1ra) (p=.002) and C-Reactive protein (CRP) (p=.036) were found in cases compared to controls. No differences were observed for interleukin-6 (IL-6), soluble Tumor Necrosis Factor Receptor type 1 (sTNF-R1) or neopterin. Both IL-1ra and CRP were correlated with physical but not with mental fatigue. In logistic regression analyses IL-1ra and CRP explained 3.5% and 2.8%, respectively, of the variance in chronic CRF. Single adjustments for depression, anxiety and neuroticism each raised the models' explained variance to approximately 35%. Those factors did not significantly alter the relationship between chronic CRF and IL-1ra/CRP. BMI and smoking emerged as possible confounding factors. These results indicate that chronic CRF in TCSs is associated with higher levels of circulating IL-1ra and CRP, possibly mediated by physiological morbidity. Hence, the findings lend some support to the hypothesis that low-grade inflammatory processes are involved in the pathogenesis of chronic CRF in cancer survivors.
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PMID:Levels of circulating interleukin-1 receptor antagonist and C-reactive protein in long-term survivors of testicular cancer with chronic cancer-related fatigue. 1936 38

Mutations in the frataxin gene cause dorsal root ganglion demyelination and neurodegeneration, which leads to Friedreich's ataxia. However the consequences of frataxin depletion have not been measured in dorsal root ganglia or Schwann cells. We knocked down frataxin in several neural cell lines, including two dorsal root ganglia neural lines, 2 neuronal lines, a human oligodendroglial line (HOG) and multiple Schwann cell lines and measured cell death and proliferation. Only Schwann cells demonstrated a significant decrease in viability. In addition to the death of Schwann cells, frataxin decreased proliferation in Schwann, oligodendroglia, and slightly in one neural cell line. Thus the most severe effects of frataxin deficiency were on Schwann cells, which enwrap dorsal root ganglia neurons. Microarray of frataxin-deficient Schwann cells demonstrated strong activations of inflammatory and cell death genes including interleukin-6 and Tumor Necrosis Factor which were confirmed at the mRNA and protein levels. Frataxin knockdown in Schwann cells also specifically induced inflammatory arachidonate metabolites. Anti-inflammatory and anti-apoptotic drugs significantly rescued frataxin-dependent Schwann cell toxicity. Thus, frataxin deficiency triggers inflammatory changes and death of Schwann cells that is inhibitable by inflammatory and anti-apoptotic drugs.
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PMID:Frataxin deficiency induces Schwann cell inflammation and death. 1967 82

Pulmonary morbidity and mortality resulting from exposure to fine particulate matter (PM) increases with age. The present studies analyzed potential mechanisms underlying increased susceptibility of the elderly to PM using diesel exhaust (DE) as a model. Mice (2 m and 18 m) were exposed to DE (0, 300, and 1000 microg/m(3)) for 3 h once (single) or 3 h/day for 3 days (repeated). Bronchoalveolar lavage fluid (BAL), serum and lung tissue were collected 0 and 24 h later. Exposure to DE resulted in structural alterations in the lungs of older but not younger mice, including patchy thickening of the alveolar septa and inflammatory cell localization in alveolar spaces. These effects were most pronounced 24 h after a single exposure to the higher dose of DE. Significant increases in BAL nitrogen oxides were also noted in older mice, as well as expression of lipocalin 24p3, an oxidative stress marker in the lung with no effects in younger mice. Following DE inhalation, expression of Tumor Necrosis Factor alpha (TNFalpha) was upregulated in lungs of both younger and older mice; however, this was attenuated in older animals. Whereas exposure to DE resulted in increases in lung Interleukin-6 (IL-6) expression in both older and younger mice, IL-8 increased only in older animals. In younger mice, constitutive expression of manganese superoxide dismutase (MnSOD) decreased after DE exposure, while in older mice, constitutive MnSOD was not detectable and DE had no effect on expression of this antioxidant. Taken together, these results suggest that altered generation of inflammatory mediators and MnSOD may contribute to increased susceptibility of older mice to inhaled DE.
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PMID:Pulmonary effects of inhaled diesel exhaust in aged mice. 1972 31

The objectives of this research were to confirm the effect of compounds derived from milk fermented by Lactobacillus helveticus (LH-2) on the nonspecific host defence system, and isolate and characterize the active peptides that mediate the immune response. The cell-free supernatant obtained from the fermented milk and its fractions were tested in vitro for immuno-modulating activity using murine macrophages (RAW 264.7 cell line). Cytokine production (Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-alpha), and Interleukin-1beta (IL1-beta)), nitric oxide (NO) production and phagocytosis were used as biomarkers. Macrophages stimulated with cell-free supernatant of fermented milk showed higher production of cytokines and NO compared with macrophages stimulated with LPS (Lipopolysaccharide) and a commercial immunomodulator derived from beta-casein (f54-59). Phagocytosis was observed by macrophages stimulated with the supernatant. Two of nine fractions collected from the supernatant using size exclusion chromatography produced the highest response when used to stimulate macrophages. The results of the dose-response study of the effect of the fraction with the highest stimulation effect on the production of TNF-alpha showed a direct correlation between protein concentration and TNF-alpha release. The fraction contained four novel peptides, three derived from the hydrolysis of beta-casein and one from the hydrolysis of alpha-lactalbumin. These results confirm that fermentation of milk by Lactobacillus helveticus (LH-2) results in the production of specific peptides capable of modulating macrophage activity.
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PMID:Characterization of immune-active peptides obtained from milk fermented by Lactobacillus helveticus. 2007 5

The prevalence of depression among patients diagnosed with cancer is higher than general population and is associated with faster tumor progression and shorter survival time. Cytokines whose primary function is to act as signaling molecules of the immune system have recently also been implicated in the pathogenesis of depression. The aim of present study was to investigate the relation between pro-infammatory cytokines [Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha)], depression and stressful life events in patients with acute leukemia. Twenty eight patients (18 males and 10 females) suffering from acute leukemia participated in this study. Their mean age was 33.3 +/- 12.1 years. They were subjected to psychiatric assessment using The Beck Depression Inventory (BDI), Holmes and Rahe Social Readjustment Scale, The Perceived Stress Scale (PSS) and The Brief Fatigue Inventory (BFI). Measurement of IL-6 and TNF-a genes expression in peripheral blood mononuclear cells was done using real-time PCR. Results revealed statistically significant elevation in the level of IL-6 gene expression, fatigue and perceived stress among depressed patients compared to none depressed group. The same results were obtained when comparing patients exposed to moderate or severe stressful life events compared to those exposed to none or mild stressful life events. Although, TNF-a gene expression was not associated with depression or stressful life events, it was associated with acute myeloblastic leukemia (AML). IL-6 gene expression was much higher among patients with AML than acute lymphoblastic leukemia (ALL), but the difference did not reach statistical significance. These findings support the hypothesis that IL-6 might be involved in the etiology and symptomatology of depression in cancer patients. The development of biologic therapies targeting IL-6 may raise the possibility of simultaneously countering the severe effects of depression.
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PMID:Pro-inflammatory cytokines and depression in patients with acute leukemia. 2030 66

The in vitro toxic response of spiropyrans in cellular models has not been previously addressed, despite the fact that such photoswitchable molecules have shown great potential as versatile and tunable components for bionanodevices and imaging agents. In this study, we examine the cytotoxic effects of a spiropyran, namely, 8-methoxy-6-nitro-BIPS (1',3'-dihydro-1'-ethanol-3',3'-dimethyl-8-methoxy-6-nitro-spiro(2H-1-benzopyran-2,2'-(2H)-indole) [1], in three cultured cellular models (THP-1, AGS, and A549 cell lines) by High Content Screening and Analysis (HCSA) and by enzyme-linked immunosorbent (ELISA) assays (Interleukin-6 and Tumor Necrosis Factor-alpha). The HCSA results show that low concentrations of 8-methoxy-6-nitro-BIPS (10(-6), 10(-8), and 10(-9) M) do not induce any cytotoxic response after 24 and 72 h exposure time, while at the highest concentrations (10(-3)and 10(-4) M) the exposure time becomes a critical parameter of the toxic response. The cell viability is reduced by 60% for THP-1 cells, 50% for AGS cells, and 40% for A549 cells at a spiropyran concentration of 10(-3) M after 24 h incubation, whereas at 72 h, the cell loss increases above 90%. Interestingly, at 10(-4) M no significant cytotoxic response is registered after 24 h exposure, where contrarily cytotoxicity is verified after 72 h. Our ELISA results show that consistently with the HCSA analysis a robust inflammatory response is present at 10(-3) M after 24 h exposure and at 10(-3) M and 10(-4) M after 72 h, in all three cell lines investigated.
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PMID:Determination of spiropyran cytotoxicity by high content screening and analysis for safe application in bionanosensing. 2080 82


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