Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High consumption of soy isoflavones in Asian diets has been correlated with a lower incidence of clinically important cases of prostate cancer. The chemopreventive properties of these diets may result from an interaction of several types of isoflavones, including genistein and daidzein. The present study investigated the effects of a soy isoflavone concentrate (ISF) on growth and gene expression profiles of PC-3 human prostate cancer cells. Trypan blue exclusion and [3H]-thymidine incorporation assays showed that ISF decreased cell viability and caused a dose-dependent inhibition of DNA synthesis, respectively, with 50% inhibition (IC50) of DNA synthesis at 52 mg/L (P = 0.05). The glucoside conjugates of genistein and daidzein in ISF were converted to bioactive free aglycones in cell culture in association with the inhibition of DNA synthesis. Flow cytometry and Western immunoblot analyses showed that ISF at 200 mg/L caused an accumulation of cells in the G2/M phase of the cell cycle (P < 0.05) and decreased cyclin A by 20% (P < 0.05), respectively. The effect of ISF on the gene expression profile of PC-3 cells was analyzed using Affymetrix oligonucleotide DNA microarrays that interrogate approximately 17,000 human genes. Of the 75 genes altered by ISF, 28 were upregulated and 47 were downregulated (P < 0.05). Further analysis showed that IL-8, matrix metalloproteinase 13, inhibin beta A, follistatin, and fibronectin mRNA levels were significantly reduced, whereas the expression of p21(CIP1), a major cell cycle inhibitory protein, was increased. The effects of ISF on the expression of IL-8 and p21(CIP1) mRNA and protein were validated at high and low ISF concentrations. Our data show that ISF inhibits the growth of PC-3 cells through modulation of cell cycle progression and the expression of genes involved in cell cycle regulation, metastasis, and angiogenesis.
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PMID:Soy isoflavones alter expression of genes associated with cancer progression, including interleukin-8, in androgen-independent PC-3 human prostate cancer cells. 1636 62

Recognition of conserved bacterial structures called pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), may lead to induction of a variety of "early immediate genes" such as chemokines. In the current study, we have in an ex vivo whole blood model studied the induction of the chemokines MIP-1alpha, MCP-1 and IL-8 by various PAMPs. The rate of appearance of Escherichia coli-Lipopolysaccharide (LPS) induced chemokines differed. The production of MIP-1alpha and IL-8 was after 1 h of stimulation significantly higher when compared to unstimulated whole blood, whereas MCP-1 was not significantly elevated until after 3 h. At peak levels the MIP-1alpha concentration induced by E. coli-LPS was 3-5-fold higher than MCP-1 and IL-8. By specific cell depletion, we demonstrated that all three chemokines were mainly produced by monocytes. However, the mRNA results showed that IL-8 was induced in both monocytes and granulocytes. The production of all three chemokines, induced by the E. coli-LPS and Neisseria meningitidis-LPS, was significantly inhibited by antibodies against CD14 and TLR4, implying these receptors to be of importance for the effects of LPS in whole blood. The chemokine production induced by lipoteichoic acid (LTA) and non-mannose-capped lipoarabinomannan (AraLAM) was, however, less efficiently blocked by antibodies against CD14 and TLR2. E. coli-LPS and LTA induced a dose-dependent increase of CD14, TLR2 and TLR4 expression on monocytes in whole blood. These data show that PAMPs may induce chemokine production in whole blood and that antibodies against PRRs inhibit the production to different extent.
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PMID:Chemokine production and pattern recognition receptor (PRR) expression in whole blood stimulated with pathogen-associated molecular patterns (PAMPs). 1640 58

A tube culture system was designed for measurement of ethylene evolved by the phytopathogenic bacterium, Pseudomonas solanacearum. The system consisted of 10 glass tubes joined together in series and coated on the inside surface with a dextrose-peptone-casamino acids agar medium. The system provided a large surface for bacterial growth in relation to the volume of air. The system was seeded with a bacterial suspension (7 x 10(8) cells/ml) drawn through all the tubes by vacuum applied at one end and was then placed in a water bath at 30 C. Air was pumped through the system at 3 ml/min; the outlet was connected directly to the inlet port of a gas sampling loop and ethylene in the sample was determined by gas chromatography.Maximum rate of ethylene production for a fluidal, virulent isolate of P. solanacearum (K60) was 5.5 x 10(-9) moles/min and occurred at the end of lag phase and beginning of stationary phase. Three other fluidal isolates produced ethylene at relatively low rates (2.4-6.4% that of K60). Avirulent, butyrous variants of these isolates grew as well as the virulent forms in most cases, but ethylene production rates per cell were much lower for the avirulent than for the virulent forms. Loss of virulence appears to be accompanied by lower ethylene production.Peak CO(2) production (14.5 mumoles/min) and O(2) consumption (11.7 mumoles/min) for isolate K60 also occurred at the time when the bacterial culture was entering stationary phase. The concentrations of O(2) (11%) and CO(2) (11%) in air present at this time were thought to be neither limiting nor inhibitory to bacterial growth.
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PMID:Technique for the Determination of the Rate of Ethylene Production by Pseudomonas solanacearum. 1665 72

One of the most significant risk factors associated with the development of skin disease is exposure to UVB radiation from the sun. In particular, UVB light can activate inflammatory and apoptotic pathways, leading to skin damage. Anthocyanins, a group of flavonoids present in many common vegetable foods, are known for their chemopreventive activity. The aim of this study was to evaluate the efficacy of cyanidin-3-O-glucoside (C3G) on modulation of cellular responses following exposure to UVB doses in human keratinocytes (HaCaT). In our study, UVB-exposed cells showed significant increase of the translocation of transcription factors NF-kB and AP-1, overexpression of the proinflammatory cytokine IL-8, cleavage of procaspase-3 (a key step in apoptotic pathway), and DNA fragmentation. All these effects elicited by UVB exposure were clearly inhibited by pretreating HaCaT cells with C3G. In conclusion, our data demonstrate that C3G can protect skin cells against the adverse effects of UVB radiation and suggest that it might successfully be employed as a skin photoprotective agent.
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PMID:Effect of cyanidin-3-O-glucoside on UVB-induced response in human keratinocytes. 1671 32

The glycolytic inhibitor 2-deoxy-D-glucose (2-DG) has been shown to enhance the cell death induced by radiation and other DNA damaging agents selectively in cells with high rates of glycolysis, like cancer cells. While energy linked modification of DNA and cellular repair processes have been suggested as possible mechanisms of sensitization, other effects such as global stress response cannot be excluded. In this pilot study, we have investigated the effect of 2-DG and radiation on the transcriptome in an attempt to elucidate how 2-DG impacts gene expression in undamaged verses irradiation (IR) damaged cells using a human malignant glioma cell line, U-87. Exponentially growing U-87 cells were exposed to various combinations of 2-DG and X-rays and total RNA was isolated four hours after exposure. Gene expression changes were elucidated using Affymetrix GeneChips. As expected, U-87 cells treated with 2-DG showed activation of several endoplasmic reticulum stress response genes. Selective RT-PCR and Western blotting confirmed these gene alterations. Given that glucose deprivation leads to p53 activation and 2-DG led to activation of p53 response genes in our present study (e.g., PMAIP1 and GADD45A), we examined the impact of transient p53 knockdown and observed that induction of PMAIP1 and GADD45A appear to be via p53-independent mechanisms. The majority of gene alterations seen with IR-treatment alone were consistent with previous reports. While most gene alterations seen with 2-DG and IR dual treatment were confirmed in the gene profiles seen with individual (2-DG or IR) treatments, several genes appeared differentially regulated between IR and 2-DG (e.g., DUSP8, IL8, GADD45B). Additionally, gene expression patterns suggested alterations in cell cycle regulation, apoptosis, and cytokine signaling pathways. Taken together, this study provides new insights into how the transcriptome of tumor cells are likely to be affected by a combined stress caused by IR and 2-DG.
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PMID:Altered gene expression induced by ionizing radiation and glycolytic inhibitor 2-deoxy-glucose in a human glioma cell line: implications for radio sensitization. 1688 Jul 34

Intestinal epithelial cells (IECs) have been known to produce galactose-alpha1,4-galactose-beta1,4-glucose ceramide (Gb3) which plays a pivotal role in the mucosal immune response. In particular, Shiga-like toxins (Stx) can induce apoptosis of IECs in the development of hemolytic uremic syndrome (HUS) through binding on Gb3. Therefore, it has been hypothesized that down-regulation of Gb3 (or binding of Stx) prevents Stx from damaging in IECs. This study investigated whether curcumin, having various biological properties such as being anti-bacterial, anti-viral and anti-cancer, could decrease binding of Stx and the related signal pathway. Curcumin significantly inhibited the binding of Stx and the production of Gb3 synthase (GalT6) mRNA in HT29 IECs stimulated with TNF-alpha and IL-1beta. Additionally, curcumin was able to inhibit mitogen-activated protein kinases (MAPKs), such as p38 and JNK, but not ERK1/2, degradation of IkappaB or translocation of NF-kappaB p65. Furthermore, curcumin significantly attenuated Stx-1 induced cell death and IL-8 expression. In summary, these data link Gb3 expression in HT29 cells stimulated with TNF-alpha and IL-1beta and suggest that blocking of Stx-binding by curcumin may prevent the Stx-associated HUS.
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PMID:Curcumin decreases binding of Shiga-like toxin-1B on human intestinal epithelial cell line HT29 stimulated with TNF-alpha and IL-1beta: suppression of p38, JNK and NF-kappaB p65 as potential targets. 1681 91

The mechanism of viral transmission across the mucosal barrier is poorly understood. Using the endometrial epithelium-derived cell line HEC-1A, we found that the cells are capable of sequestering large numbers of HIV-1 particles but are refractory to cell-free viral infection. The removal of heparan sulfate moieties of cell-surface proteoglycans (HSPG) from the apical pole of HEC-1A accounted for at least 60% of both R5- and X4-HIV-1 attachment, showing their important implication in viral attachment. HEC-1A cells also have the capacity to endocytose a weak proportion of the attached virus and pass it along to underlying cells. Fucose, N-acetylglucosamine and mannosylated-residues inhibited the transcytosis of some virus isolates, suggesting that mannose receptors can be implicated on the both R5- and X4-HIV-1 transcytosis. The inhibition of HIV transcytosis by blocking CCR5 mAb suggests the implication of specific interaction between the viral gp120 and sulfated moiety of syndecans during the transcytosis of mostly R5- and X4-HIV-1. At the basolateral pole of HEC-1A, HSPG sequestered X4- and not R5-HIV-1, highlighting the important role of HEC-1A as an X4 virus reservoir. The cell-free virus particles that have transcytosed could infect activated T cells but with a weaker efficiency than virus that had not transcytosed. The specific stimulation of HEC-1A by R5-HIV-1 increased the release of monocytes/chemokines-attracting chemokines (IL-8 and GR0) and proinflammatory cytokines (TNF-beta and IL-1alpha) that enhanced the production of virus by activated T cells. This study suggests that R5 and X4 viruses can differentially use epithelial cells to ensure their own spread.
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PMID:R5- and X4-HIV-1 use differentially the endometrial epithelial cells HEC-1A to ensure their own spread: implication for mechanisms of sexual transmission. 1693 8

Interaction with the unique fungus Pneumocystis (Pc) promotes IL-8 release by human alveolar macrophages (AM), although the receptor(s) mediating IL-8 release have not been identified. TLR2 recognizes fungal components and mediates release of host defense cytokines and chemokines, although whether TLR2 mediates signaling in response to Pc is not known. In the current study, Pc induced IL-8 release by human AM, and AM pretreatment with anti-TLR2 neutralizing antibody reduced IL-8 release. However, in nonphagocytic human embryonic kidney (HEK)293 cells transfected with human TLR2 cDNA, incubation with Pc did not induce IL-8 release, whereas these same cells released IL-8 in response to the TLR2 agonist lipoteichoic acid. Targeted gene silencing of AM mannose receptors (MR; phagocytic receptors for Pc) using small interfering RNA also reduced Pc-mediated IL-8 release in human AM. However, HEK293 cells transfected with human MR cDNA alone did not release IL-8 in response to Pc. In contrast, HEK293 cells cotransfected with human TLR2 and human MR cDNA released IL-8 in response to Pc. In human AM, Pc promoted direct interaction of MR and TLR2, IL-8 release was reduced markedly upon simultaneous blocking of TLR2 and gene silencing of MR, and IL-8 release was dependent in part on transcription factor NF-kappaB and ERK1/2 and JNK MAPKs. These studies demonstrate that Pc-mediated IL-8 release by human AM requires the coexpression of MR and TLR2 and further supports the concept that combinatorial interactions of macrophage innate receptors provide specificity of host defense cell responses to infectious challenge.
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PMID:Pneumocystis-mediated IL-8 release by macrophages requires coexpression of mannose receptors and TLR2. 1702 Sep 28

In Korea and China, Ulmus davidiana var. japonica has been used as a traditional oriental medicine for the treatment of difficulty in urination, skin inflammation, etc. In order to investigate the potential of a polysaccharide extract from Ulmus davidiana var. japonica as a cosmetic ingredient, we measured its moisturizing effect, photo-induced cytotoxicity, and anti-inflammatory effect. After hydrolysis, HPLC experiments showed that the composition of the polysaccharide extract was mainly rhamnose, galactose, and glucose. The molecular weight of the obtained Ulmus davidiana root extract was 20,000. The intrinsic viscosity was 90 dl/g. In a moisturizing test conducted through the measurement of water loss in a desiccator and of moisture content with a Corneometer CM820, Ulmus davidiana root extract showed almost the same moisturizing effect as hyaluronic acid. In an assay for inhibition of the H(2)O(2)-activated release of PGE2, IL-6, and IL-8 in normal human fibroblast cell lines, Ulmus davidiana root extract showed an inhibitory activity of PGE2 release in a dose-dependent manner (up to 85.9% at a concentration of 0.1%). The percent inhibition of the release of IL-6 was in the range of 45.6% to 64.5% (H(2)O(2) was used as the positive control). Moreover, the release of IL-8 was completely inhibited in the entire concentration range (>0.0025%). In a test of recovery from photo-induced damage after UVA irradiation (3 J/cm(2)), the cell recovery of human fibroblasts increased to levels two times higher than that of the positive control, which was UVA-damaged cells in the absence of Ulmus davidiana root extract (up to 60.2% at 3.0% of Ulmus davidiana root extract). In a photo-induced cytotoxicity assay in the presence of promethazine as a photosensitizer, Ulmus davidiana root extract showed approximately 48% of the increased cell viability of the control. Therefore, Ulmus davidiana root extract may be useful for the development of a cosmetic ingredient.
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PMID:Cosmeceutical properties of polysaccharides from the root bark of Ulmus davidiana var. japonica. 1711 Oct 70

The lectin from the legume Vatairea macrocarpa is a galactose/N-acetylgalactosamine binding protein that induced cellular inflammatory response mediated by resident cells. This study investigated which inflammatory mediators would be released from lectin-activated cells. The intraperitoneal injection in rats of the supernatant from cultured macrophages, but not from mast cells, stimulated with lectin induced a time- and dose-dependent release of a neutrophil chemotactic factor, termed MNCF-VML. Pharmacological modulation with dexamethasone inhibited both the lectin-induced chemotactic activity in vivo and also the lectin-induced release of MNCF-VML into the supernatant of cultured macrophages. Cyclooxygenase and lipoxygenase metabolites are apparently not involved in the action of this factor or its release, since indomethacin or MK886 were unable to affect the lectin response. The molecular weight of MNCF-VML was found to be greater than 5 kDa, which led to the investigation of which cytokine(s) could be involved by the following approaches: (a) treatment of animals with antiserum to tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1, or IL-8 before intraperitoneal injection of lectin and (b) addition of antiserum to TNF-alpha, IL-1, or IL-8 to the supernatant of lectin-stimulated macrophages before intraperitoneal administration. Antiserum to TNF-alpha, but not IL-1 nor IL-8, inhibited the neutrophil migration induced either by lectin or MNCF-VML. Our data suggest that neutrophil migration induced by V. macrocarpa lectin occurs via the release of cytokines such as TNF-alpha by macrophages. Thus, this lectin may represent an important tool to better understand pathological situations where an excess of leukocytes at inflammatory sites causes tissue injury.
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PMID:Vatairea macrocarpa (Leguminosae) lectin activates cultured macrophages to release chemotactic mediators. 1717 56


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