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

We reviewed the literature related to the effects of high-dose zinc in arteriosclerosis-induced angina pectoris. Lipid peroxidation and LDL oxidation are believed to be critical for arteriosclerosis, and consequently angina pectoris. Administration of biologically available zinc was a beneficial treatment in a significant percentage of patients with severely symptomatic, inoperable atherosclerotic disease. In these patients, there was no difference in zinc concentration between patients with and without atherosclerosis in whole blood, erythocytes or hair, but there was a major difference between normal aorta and diseased aortas (40.6 ppm zinc in normal aorta vs. 23.2 ppm zinc in atherosclerotic aorta, 40.6 ppm zinc in normal aorta vs. 19.4 ppm zinc in atherosclerotic aneurysm aorta, and no difference between normal and aneurysm aorta), although copper was low in aneurysm aorta. Medication with high-dose zinc sulfate to raise zinc serum concentrations from 95 to 177 microg/dl resulted in objective improvement in 12 of 16 of these patients, including a patient that also had Raynaud's disease. Long term environmental exposure to zinc resulted in a 40% reduction in the incidence of angina of effort compared to people not exposed to environmental zinc (P<0.01) and a 40% reduction in the incidence of probable ischemia in exercise (P<0.001). Lead had no effect while cadmium exposure resulted in more than tripling the incidence of angina of effort (P<0.001). The antioxidative action of zinc prevents oxidation of LDL cholesterol and consequently stops the main mechanism of atherogenesis. Zinc blocks calcium and its several actions on atherogenesis. Increased amounts of cytotoxic cytokines such as TNF-alpha, IL-beta and IL-8, often produced in the elderly, are blocked by high-dose zinc. We hypothesize that higher serum concentrations of LDL cholesterol resulting from administration of 300 mg of zinc per day is caused by a release of low density cholesterol from cardiovascular tissues, beneficially flushing it into the serum where it is readily observed, thus decreasing arteriosclerosis, increasing circulation, terminating angina pectoris and restoring more youthful cardiac function. Although prevention of cholesterol-induced arteriosclerosis by zinc is predicted from findings related to oxidative stress and lipid peroxidation, removal of LDL might be attributable to action of ionic zinc on ICAM inhibition. In stark contrast to current practice, high-dose zinc should be considered as basic in the strategy of prophylaxis and therapy of the atherosclerosis process to terminate angina pectoris and restore youthful cardiac function.
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PMID:High-dose zinc to terminate angina pectoris: a review and hypothesis for action by ICAM inhibition. 1608 66

Heparan sulfate proteoglycans (HSPGs), via their interactions with numerous effector molecules such as FGF-2, IL-8, and VEGF, regulate the biological activity of cells by acting as co-receptors that promote signaling. The extent and nature of their role as co-receptors is often misregulated in cancer as manifested by alterations in HSPG structure and expression level. This misregulation of HSPGs can aid in promoting the malignant phenotype. In addition to expression-related changes in HSPGs, recent discoveries indicate that HSPGs localized within the tumor microenvironment can be attacked by enzymes that alter proteoglycan structure resulting in dramatic effects on tumor growth and metastasis. This review focuses on remodeling of HSPGs by three distinct mechanisms that occur in vivo; (i) shedding of proteoglycan extracellular domains from cell surfaces, (ii) fragmentation of heparan sulfate chains by heparanase, and (iii) removal of sulfates from the 6-O position of heparan sulfate chains by extracellular sulfatases. Assessing or monitoring the remodeling of HSPGs has important implications for tumor diagnosis and patient prognosis while therapeutic manipulation of the remodeling process represents an exciting new possibility for treating cancer.
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PMID:Enzymatic remodeling of heparan sulfate proteoglycans within the tumor microenvironment: growth regulation and the prospect of new cancer therapies. 1614 80

Micromass cultures represent a convenient means of studying chondrocyte physiology in the context of a tridimensional culture model. In this study, we present the first ultrastructural analysis of the distribution and organization of the extracellular components in micromasses in comparison with their cartilaginous counterparts. Primary chondrocytes obtained from osteoarthritis patients were pelleted in micromasses. Transmission electron microscopy and immunofluorescence were used to evaluate the distribution of major extracellular matrix proteins, i.e., aggrecan, chondroitin-4-sulfate, chondroitin-6-sulfate, and collagen I and II. Both approaches revealed a number of morphological features shared by micromass and cartilage chondrocytes. In particular, in micromasses, chondrocytes are in close contact with an organized extracellular matrix that adequately mimics that of cartilage. Cells were observed to establish specialized junctions for cell-extracellular matrix crosstalk. Noteworthy, cells seem endowed in a chondroitin sulfate-rich microenvironment, and thus possibly ensuring the immobilization of chemokines, a family of molecules emerging in osteoarthritis pathogenesis, in a haptotactic-like gradient to the chondrocytes, which facilitates the binding to their receptors. To determine the suitability of this model to investigate osteoarthritis pathogenesis, a potential apoptotic stimulus (endothelial IL-8) was used, and ultrastructural analysis assessed apoptosis induction. Micromass cultures were proved to be an experimental technique providing a large number of properly differentiated chondrocytes, and thus allowing reliable biochemical and morphological studies. They represent, therefore, a novel approach to osteoarthritis investigation that promises more thorough understanding of chondrocyte physiology in osteoarthritis.
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PMID:Cell and matrix morpho-functional analysis in chondrocyte micromasses. 1617 90

In vitro binding assays were used to study the possible role of a cell wall agglutinin in the attachment to plant cell walls of avirulent strains of the wilt pathogen, Pseudomonas solanacearum. In a nitrocellulose filter assay, radioactively labeled lipopolysaccharide (LPS) from the virulent strain, K60, and the avirulent strain, B1, and extracellular polysaccharide (EPS) from K60 were bound quantitatively by the agglutinin extracted from Katahdin potato tubers. The LPS from B1 had significantly greater agglutinin-binding affinity than that from K60 but not after treatment with deoxycholate, which improved solubility. Highly purified chitotetraose did not inhibit binding of K60 LPS to agglutinin, but binding was inhibited by EPS as well as by diverse anionic polymers (DNA, dextran sulfate, xanthan). Binding of agglutinin to EPS and LPS was inhibited at ionic strengths greater than 0.03 and 0.15 M, respectively. It was concluded that electrostatic charge-charge interactions could account for binding of LPS and EPS to potato agglutinin.
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PMID:Interaction of Pseudomonas solanacearum Lipopolysaccharide and Extracellular Polysaccharide with Agglutinin from Potato Tubers. 1634 87

Lipopolysaccharide (LPS)-defective mutants of Pseudomonas solanacearum were used to test the hypothesis that differences in LPS structure are associated with the ability or inability of different strains to induce a hypersensitive response (HR) in tobacco. To obtain these mutants, LPS-specific bacteriophage of P. solanacearum were isolated and used to select phage-resistant mutants of the virulent, non-HR-inducing strain K60. The LPS of 24 of these mutants was purified and compared with that of K60 and its HR-inducing variant, B1. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, LPS from K60 and other smooth strains separated into many evenly spaced bands that migrated slowly, whereas LPS from B1 and most phage-resistant strains separated into one to three bands that migrated rapidly. Carbohydrate analysis showed that the LPS of the phage-resistant strains lacked O-antigen sugars (rhamnose, xylose, and N-acetylglucosamine) and could be grouped into (i) those that had all core sugars (rhamnose, glucose, heptose, and 2-keto-3-deoxyoctonate), (ii) those that had no core rhamnose, and (iii) those that lacked all core sugars except for 2-keto-3-deoxyoctonate. The LPS composition of 10 of the rough, phage-resistant mutants was similar to that of the HR-inducing strain, B1, yet none of them induced the HR. Only 2 of 13 mutant strains tested caused wilting of tobacco, and these had rough LPS but produced large amounts of extracellular polysaccharide, unlike most LPS-defective mutants. The evidence did not support the hypothesis that the initial interaction between rough LPS and tobacco cell walls is the determining factor in HR initiation.
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PMID:Lipopolysaccharide-Defective Mutants of the Wilt Pathogen Pseudomonas solanacearum. 1634 3

Preterm labor is associated with the release of various cytokines that play an important role in its pathophysiology. In preterm labor, tocolytics are used to inhibit uterine contractions and prolong gestation. We tested the hypothesis that tocolytics alter endotoxin-induced interleukin (IL-8) production from amniotic and decidual cells in vitro. Amniotic and decidual cells were isolated from patients undergoing elective repeat cesarean section at term. Cells were grown in tissue culture flasks. Cells were subsequently incubated with 100 ng/ml of endotoxin in 24 well plates in the presence of increasing concentrations of magnesium sulfate, nifedipine and terbutaline. After 24 h, IL-8 levels in each well were measured by ELISA. Endotoxin caused a significant elevation in IL-8 production in both amniotic and decidual cells. Magnesium sulfate dose dependently inhibited the endotoxin-stimulated IL-8 production in both decidual and amniotic cells. However, nifedipine and terbutaline did not significantly affect IL-8 production in either cell type. In conclusion, magnesium sulfate differentially suppresses endotoxin-stimulated IL-8 production in amniotic and decidual cells in vitro. The cellular mechanisms of this suppression and its clinical relevance in the setting of preterm labor merit further investigation.
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PMID:Effect of tocolytics on interleukin-8 production by human amniotic and decidual cells. 1638 5

IL-22 is produced by activated T cells and signals through a receptor complex consisting of IL-22R1 and IL-10R2. The aim of this study was to analyze IL-22 receptor expression, signal transduction, and specific biological functions of this cytokine system in intestinal epithelial cells (IEC). Expression studies were performed by RT-PCR. Signal transduction was analyzed by Western blot experiments, cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and Fas-induced apoptosis by flow cytometry. IEC migration was studied in wounding assays. The IEC lines Caco-2, DLD-1, SW480, HCT116, and HT-29 express both IL-22 receptor subunits IL-22R1 and IL-10R2. Stimulation with TNF-alpha, IL-1beta, and LPS significantly upregulated IL-22R1 without affecting IL-10R2 mRNA expression. IL-22 binding to its receptor complex activates STAT1/3, Akt, ERK1/2, and SAPK/JNK MAP kinases. IL-22 significantly increased cell proliferation (P = 0.002) and phosphatidylinsitol 3-kinase-dependent IEC cell migration (P < 0.00001) as well as mRNA expression of TNF-alpha, IL-8, and human beta-defensin-2. IL-22 had no effect on Fas-induced apoptosis. IL-22 mRNA expression was increased in inflamed colonic lesions of patients with Crohn's disease and correlated highly with the IL-8 expression in these lesions (r = 0.840). Moreover, IL-22 expression was increased in murine dextran sulfate sodium-induced colitis. IEC express functional receptors for IL-22, which increases the expression of proinflammatory cytokines and promotes the innate immune response by increased defensin expression. Moreover, our data indicate intestinal barrier functions for this cytokine-promoting IEC migration, which suggests an important function in intestinal inflammation and wound healing. IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and IEC migration.
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PMID:IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. 1653 74

Ghrelin, a newly identified gastric peptide, is known for its potent activity in growth hormone (GH) release and appetite. Although ghrelin is involved in several other responses such as stress and intestinal motility, its potential role in intestinal inflammation is not clear. Here, we show that expression of ghrelin and its receptor mRNA is significantly increased during acute experimental colitis in mice injected intracolonically with trinitrobenzene sulfate (TNBS). We found by PCR that ghrelin receptor mRNA is expressed in non-transformed human colonic epithelial NCM460 cells. Exposure of NCM460 cells stably transfected with ghrelin receptor mRNA to ghrelin, increased IkappaBalpha phosphorylation and its subsequent degradation. In addition, ghrelin stimulated NF-kappaB-binding activity and NF-kappaB p65 subunit phosphorylation, and induced IL-8 promoter activity and IL-8 protein secretion. Furthermore, our data show that ghrelin-induced IkappaBalpha and p65 phosphorylation was markedly reduced by pharmacological inhibitors of intracellular calcium mobilization (BAPTA/AM) and protein kinase C (GF 109203X). Pretreatment with BAPTA/AM or GF109203X also significantly attenuated ghrelin-induced IL-8 production. Together, our results strongly suggest that ghrelin may be a proinflammatory peptide in the colon. Ghrelin may participate in the pathophysiology of colonic inflammation by inducing PKC-dependent NF-kappaB activation and IL-8 production at the colonocyte level.
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PMID:Ghrelin stimulates interleukin-8 gene expression through protein kinase C-mediated NF-kappaB pathway in human colonic epithelial cells. 1655 51

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.
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PMID:Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate. 1678 54

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


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