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)

Airborne particulate matter (PM) has a complex composition, and the relative contribution of different compounds to PM-induced effects is only partly understood. The present study compared the capability of selected components commonly found in PM, to induce pro-inflammatory responses in lung epithelial cells. Ultrafine carbon black (ufCB), ZnCl(2), FeSO(4), 1-nitropyrene (1-NP), lipopolysaccharide (LPS), and crystalline silica (positive control) were screened for effects on the expression of 84 inflammation-related genes in the bronchial epithelial cell line, BEAS-2B. A total of 22 genes were up-regulated by one or more of the tested compounds, and 5 cytokine and 11 chemokine genes were selected for further studies. After 10h exposure, silica induced significantly increased expression of CCL20, CXCL1/-3/-8/-10/-11, lymphotoxin (LT)beta and interleukin (IL)-6; ufCB induced CXCL8/-10 and -11; ZnCl(2) induced CCL11/-20/-26, CXCL1/-5/-8/-14 and tumor necrosis factor (TNF)-alpha; FeSO(4) induced a weak up-regulation of CXCL8 and TNF-alpha; LPS induced CCL20, CXCL1/-5/-8/-10/-11, LTbeta and IL-6; and 1-NP induced expression of CCL20, CXCL1/-3/-8, TNF-alpha and IL-6. Despite obvious differences, all compounds induced response-patterns that correlated relatively well with that of silica, the positive control. The predominant response appeared to be increased gene expression of neutrophil-recruiting CXC-chemokines. CXCL8 was the only gene induced by all tested PM-components, the most up-regulated on average, and also dominating the gene-expression patterns induced by coarse PM. The data show quantitative, and to a certain extent qualitative differences in cytokine/chemokine gene-expression profiles of the compounds tested. However, there were also striking similarities in the response-patterns induced by these physically/chemically widely different compounds.
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PMID:Cytokine and chemokine expression patterns in lung epithelial cells exposed to components characteristic of particulate air pollution. 1942 42

Acetylcholine is the primary parasympathetic neurotransmitter in the airways and is known to cause bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine also regulates aspects of remodelling and inflammation through its action on muscarinic receptors. In the present study, we aimed to determine the effects of muscarinic receptor stimulation on cytokine production by human airway smooth muscle cells (primary and immortalised cell lines). The muscarinic receptor agonists carbachol and methacholine both induced modest effects on basal interleukin (IL)-8 and -6 secretion, whereas the secretion of RANTES, eotaxin, vascular endothelial growth factor-A and monocyte chemoattractant protein-1 was not affected. Secretion of IL-8 and -6 was only observed in immortalised airway smooth muscle cells that express muscarinic M3 receptors. In these cells, methacholine also significantly augmented IL-8 secretion in combination with cigarette smoke extract in a synergistic manner, whereas synergistic effects on IL-6 secretion were not significant. Muscarinic M3 receptors were the primary subtype involved in augmenting cigarette smoke extract-induced IL-8 secretion, as only tiotropium bromide and muscarinic M3 receptor subtype selective antagonists abrogated the effects of methacholine. Collectively, these results indicate that muscarinic M3 receptor stimulation augments cigarette smoke extract-induced cytokine production by airway smooth muscle. This interaction could be of importance in patients with chronic obstructive pulmonary disease.
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PMID:Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells. 1946 Jul 89

There is ample evidence that asthma is mediated by oxidative stress and that viral infection, which is associated with asthma onset and exacerbation in infants, acts as one type of oxidative stress. The goal of this study was to determine whether respiratory syncytial virus (RSV) induces oxidative stress in cultured A549 human airway epithelial cells and normal human bronchial epithelial cells (NHBE), and whether such RSV-induced oxidative stress can induce airway inflammation. To evaluate the direct effect of RSV infection as an oxidative stressor, the intracellular levels of reduced glutathione (GSH) or oxidized glutathione (GSSG) were measured. Their ratio (GSH/GSSG) was calculated to indicate intracellular oxidation-reduction (redox) status in A549 and NHBE. To evaluate the extent to which glutathione redox regulation affected cytokine/chemokine production, the effect of pretreatment with a reductive agent, glutathione monoethyl ester (GSH-OEt) and RSV-specific monoclonal antibody was thus studied. RSV acted as a potent oxidative stressor on the intracellular glutathione redox state in human airway epithelial cells, activating signals to increase the production of cytokine/chemokine. Pretreatment with GSH-OEt significantly suppressed RSV-induced time-dependent changes in the intracellular redox state, and also suppressed RSV-induced up-regulation of epithelial cell-derived IL-8, IL-6 and eotaxin production, as well as RSV-specific monoclonal antibody. RSV-induced oxidative stress is likely to contribute to the perpetuation and amplification of the inflammatory response. Therapeutic intervention against oxidative stress might therefore be beneficial as adjunctive therapies for respiratory disorders that are caused by an RSV infection.
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PMID:RS virus-induced inflammation and the intracellular glutathione redox state in cultured human airway epithelial cells. 1954 75

Clinical and experimental studies have established eosinophilia as a sign of allergic disorders. Activation of eosinophils in the airways is believed to cause epithelial tissue injury, contraction of airway smooth muscle and increased bronchial responsiveness. As part of the search for new antiasthmatic agents produced by medicinal plants, the effects of 270 standardized medicinal plant extracts on cytokine-activated A549 human lung epithelial cells were evaluated. After several rounds of activity-guided screening, the new natural compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione (PPY), was isolated from Vitex rotundifolia L. To elucidate the mechanism by which the anti-asthmatic responses of PPY occurred in vitro, lung epithelial cells (A549 cell) were stimulated with TNF-alpha, IL-4 and IL-1beta to induce the expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. PPY treatments reduced the expression of eotaxin, IL-8, IL-16 and VCAM-1 mRNA significantly. Additionally, PPY reduced eotaxin secretion in a dose-dependent manner and significantly inhibited eosinophil migration toward A549 medium. In addition, PPY treatment suppressed the phosphorylation of p65 and ERK1/2, suggesting that it can inhibit the MAPK/NF-KB pathway. To clarify the anti-inflammatory and antiasthmatic effects of PPY in vivo, we examined the influence of PPY on the development of pulmonary eosinophilic inflammation in a murine model of asthma. To accomplish this, mice were sensitized and challenged with ovalbumin (OVA) and then examined for the following typical asthmatic reactions: an increase in the number of eosinophils in BALF; the presence of Th2 cytokines such as IL-4 and IL-5 in the BALF; the presence of allergen-specific IgE in the serum; and a marked influx of inflammatory cells into the lung. Taken together, our results revealed that PPY exerts profound inhibitory effects on the accumulation of eosinophils into the airways while reducing the levels of IL-4, IL-5, and IL-13 in the BALF. Therefore, these results suggest that PPY may be useful as a new therapeutic drug for the treatment of allergic asthma.
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PMID:A new compound, 1H,8H-pyrano[3,4-c]pyran-1,8-dione, suppresses airway epithelial cell inflammatory responses in a murine model of asthma. 1982 76

Ixodid ticks require comparatively large bloodmeals for their development and survival. Blood-feeding elicits signaling events in the host leading to wound healing responses (hemostasis, inflammation, and tissue repair) and immunity. Bioactive molecules present in tick saliva sabotage these host responses at several levels. One of them is neutralization of cellular communication by binding of specific saliva molecules to cytokines that have important roles in innate and adaptive immunity. Chemokines are a subset of cytokines having chemotactic activities. We show anti-chemokine activities in salivary gland extracts (SGE) of adult Rhipicephalus appendiculatus ticks against human chemokines CXCL8, CCL2, CCL3, CCL5, and CCL11. At comparable protein concentrations, male Ixodes ricinus SGE showed activity against all the chemokines; SGE of female I. ricinus had comparatively lower levels of activity against all the chemokines but no detectable activity against CCL5 and CCL11. However, when the equivalent of a single pair of salivary glands was tested, male I. ricinus showed little or no activity against CCL3 and CCL5. No fundamental differences in activity were observed against mouse compared with human chemokines. A comparison with previously published data for Dermacentor reticulatus and Amblyomma variegatum indicates that the level of anti-cytokine activity depends on the species, developmental stage (adult or nymph), and amount of SGE used, as well as on the number of days the tick has been feeding.
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PMID:Anti-chemokine activities of ixodid ticks depend on tick species, developmental stage, and duration of feeding. 1983 89

The purpose of our study was to investigate whether tumor necrosis factor (TNF)-alpha correlates with eosinophilic inflammation that occurs during a lower respiratory tract infection with the respiratory syncytial virus (RSV) in children. Sixty children with RSV bronchiolitis (RSV group) and 20 healthy children with no respiratory symptoms (Control group) were enrolled. We measured the nasal lavage fluid (NLF) Th2 cytokine (IL-5), proinflammatory cytokine (TNF-alpha, IL-8), eosinophil-active cytokine [granulocyte-macrophage colony stimulating factor (GM-CSF), IFN-gamma], and eosinophil-active chemokine (eotaxin, regulated on activation normal T cell excreted and secreted) levels for both groups. We also measured serum eosinophil-degranulation product (eosinophil-derived neurotoxin; EDN, eosinophil cationic protein; ECP) levels from RSV group. TNF-alpha, IL-8, GM-CSF, IFN-gamma, and eotaxin levels were significantly higher in the RSV group compared with the Control group. TNF-alpha correlated with GM-CSF (r = 0.87, p < 0.0001), IFN-gamma (r = 0.92, p < 0.0001), eotaxin (r = 0.64, p < 0.0001), and IL-8 (r = 0.84, p < 0.0001). TNF-alpha may have an important role in eosinophilic inflammation of airways in children with RSV bronchiolitis.
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PMID:The role of TNF-alpha in eosinophilic inflammation associated with RSV bronchiolitis. 2008 64

Expression of PAR, the thrombin receptor, is elevated in smooth muscle cell-rich areas in atherosclerotic plaques, where the cells change to proinflammatory or synthetic phenotype. In this study we investigated whether thrombin promotes a proinflammatory phenotype in vascular smooth muscle cell (VSMC), characterized by increased cytokine and chemokine synthesis. Thrombin not only elevated transcripts for IL-6, CXCL8, and CCL11 genes but also enhanced release of IL-6 and CXCL8 protein from human aortic smooth muscle cell (HAoSMC). Thrombin activated Akt, PKC and MAPK in HAoSMC, and thrombin-mediated expression of IL-6 and CXCL8 was significantly inhibited by LY294002, AKT IV, RO318220, and GF109203X as well as by diphenyleneiodium at the messenger RNA and the protein levels. SB202129 and U0126 also significantly attenuated thrombin-mediated release of IL-6 and CXCL8 proteins from HAoSMC. These results indicate that thrombin promotes proinflammatory phenotype in human VSMC and that PI3K, Akt, PKC, NADPH oxidase, and MAPK are involved in that process. We propose that activation VSMC in response to thrombin after endothelial injury and/or thrombus formation will enhance inflammation in vasculature.
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PMID:Thrombin promotes proinflammatory phenotype in human vascular smooth muscle cell. 2045 99

Thymic stromal lymphopoietin (TSLP) plays a pivotal role in allergic diseases such as asthma, chronic obstructive pulmonary disease, and atopic dermatitis. Enhanced TSLP expression has been detected in asthmatic airways that correlated with both the expression of Th2-attracting chemokines and with disease severity. Although cumulative evidence suggests that human airway smooth muscle (HASM) cells can initiate or perpetuate the airway inflammation by secreting a variety of inflammatory cell products such as cytokines and chemokines, the role of TSLP in this pathway is not known. In the current study, we sought to investigate whether HASM cells express the TSLP receptor (TSLPR) and whether it is functional. We first demonstrated that primary HASM cells express the transcript and protein of both TSLPR subunits (TSLPR and IL-7Ralpha). Functionally, TSLPR-mediated HASM activation induced a significant increase in CXC (IL-8/CXCL8), CC (eotaxin-1/CCL11) chemokines, and proinflammatory cytokine IL-6 expression. Furthermore, using biochemical and genetic approaches, we found that TSLP-induced proinflammatory gene expression in HASM involved the transcriptional mechanisms, MAPKs (ERK1/2, p38, and JNK), and STAT3 activation. Finally, TSLPR immunoreactivity in bronchial sections from mild allergic asthmatics suggested the potential in vivo TSLP targeting of HASM. Altogether, our data suggest that the TSLPR-mediated HASM activation induces proinflammatory cytokine and chemokines release that may facilitate inflammatory immune cells recruitment in airways. In addition, it may be inferred that TSLPR is involved in the pathogenesis of allergic asthma through the activation of HASM cells by TSLP.
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PMID:Thymic stromal lymphopoietin receptor-mediated IL-6 and CC/CXC chemokines expression in human airway smooth muscle cells: role of MAPKs (ERK1/2, p38, and JNK) and STAT3 pathways. 2048 34

Human blood eosinophils exposed ex vivo to hematopoietic cytokines (e.g., IL-5 or GM-CSF) subsequently display enhanced responsiveness to numerous chemoattractants, such as chemokines, platelet-activating factor, or FMLP, through a process known as priming. Airway eosinophils, obtained by bronchoalveolar lavage after segmental Ag challenge, also exhibit enhanced responsiveness to selected chemoattractants, suggesting that they are primed during cell trafficking from the blood to the airway. Earlier work has shown that chemoattractants stimulate greater activation of ERK1 and ERK2 following IL-5 priming in vitro, thus revealing that ERK1/ERK2 activity can be a molecular readout of priming under these circumstances. Because few studies have examined the intracellular mechanisms regulating priming as it relates to human airway eosinophils, we evaluated the responsiveness of blood and airway eosinophils to chemoattractants (FMLP, platelet-activating factor, CCL11, CCL5, CXCL8) with respect to degranulation, adherence to fibronectin, or Ras-ERK signaling cascade activation. When compared with blood eosinophils, airway eosinophils exhibited greater FMLP-stimulated eosinophil-derived neurotoxin release as well as augmented FMLP- and CCL11-stimulated adherence to fibronectin. In airway eosinophils, FMLP, CCL11, and CCL5 stimulated greater activation of Ras or ERK1/ERK2 when compared with baseline. Ras activation by FMLP in blood eosinophils was also enhanced following IL-5 priming. These studies are consistent with a model of in vivo priming of eosinophils by IL-5 or related cytokines following allergen challenge, and further demonstrate the key role of priming in the chemoattractant-stimulated responses of eosinophils. These data also demonstrate the importance of the Ras-ERK signaling pathway in the regulation of eosinophil responses to chemoattractants in the airway. Human airway eosinophils respond to several chemoattractants with increased activation of the Ras-ERK cascade, eosinophil-derived neurotoxin release, and adherence to fibronectin relative to blood eosinophils.
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PMID:Human airway eosinophils respond to chemoattractants with greater eosinophil-derived neurotoxin release, adherence to fibronectin, and activation of the Ras-ERK pathway when compared with blood eosinophils. 2049 64

To elucidate the mechanisms of intractable pediatric bronchial asthma and the indication of low-dose erythromycin (EM) therapy, the serum chemokine levels of and the angiogenic factor were evaluated in 55 pediatric patients with bronchial asthma; 7.4 +/- 3.5 yr old, who had been treated with inhaled steroid, leukotriene receptor antagonist, theophylline and others for more than a year. Both the levels of interleukin (IL) 8 (p = 0.036) and vascular endothelial growth factor (VEGF) (p = 0.005) were higher in patients with severe type than those of patients with the milder type, while other chemokine levels such as serum eotaxin and MCP1 did not show the correlation with the severity of bronchial asthma. Induction of therapy with low-dose EM induced improvement of the clinical symptoms in patients with severe type and decrease of their serum chemokine levels: IL8; from 736 +/- 88 to 75 +/- 85 pg/ml (p < 0.0005), and VEGF; from 352.0 +/- 160.5 to 132.2 +/- 59.9 pg/ml (p = 0.021) within the next 6 months. Moreover, low-dose EM resulted in a decreased daily peak-trough fluctuation rate of the serum theophylline concentration; (C(max )- C(min))/C(min), from 1.3 +/- 0.5 to 0.5 +/- 0.3, which led to the maintenance of effective serum levels. These results indicated that IL8 and VEGF affect the severity of standard therapies resistance intractable bronchial asthma. Through the suppression of these chemokines and maintenance of effective theophylline levels, low-dose EM therapy improves the symptoms of bronchial asthma.
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PMID:The indication and effectiveness of low-dose erythromycin therapy in pediatric patients with bronchial asthma. 2054 25


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