UNIPROT:P10145 - FACTA Search

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)

Asthma is a chronic inflammatory disease of the airways in which many cell types play a role. Although the most important cells are eosinophils, there are suggestions that also neutrophils may play a role in asthma. The aim of the study was to measure and compare chemotactic activity of neutrophils in patients with severe asthma and with COPD. We examined 49 patients with severe asthma and 23 patients with COPD. The mean number of neutrophils in peripheral blood of 20 asthmatics with irreversible airflow obstruction was 3.96 x 10(6)/ml. The chemotactic activity of neutrophils to FMLP was 2.69 SEM +/- 0.4, to IL-8 in concentration 10-7 microg/ml - 1.64, SEM +/- 0.2, and to IL-8 in concentration 10-8 microg/ml - 1.17, SEM +/- 0.1. The mean number of neutrophils in 29 asthmatics with reversible airflow obstruction was 3.08 x 10(6)/ml. Their chemotactic activity to fMLP was 1.7, SEM +/- 0.1 to IL-8 in concentration 10-7 microg/ml - 1.51. SEM +/- 0.2, and to IL-8 in concentration 10-8 microg/ml - 1.08, SEM +/- 0.1. The mean number of neutrophils in COPD patients was 4.05 x 10(6)/ml and their chemotactic activity to FMLP was 1.9, SEM +/- 0.1 to IL-8 - 1.35, SEM +/- 0.1. All asthmatic patients were treated with inhaled corticosteroids and some of them with oral corticosteroids. Despite of that treatment the number of neutrophils isolated from patients with asthma with irreversible airflow obstruction was almost the same like in COPD patients and chemotactic activity of neutrophils in this group was the highest. We concluded that corticosteroids treatment did not diminished chemotactic activity of neutrophils isolated from patient suffering from asthma with irreversible airflow obstruction.
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PMID:[Chemotactic activity of neutrophils to fMLP and IL-8 in patients with severe asthma with reversible and irreversible airflow obstruction and in patients with chronic obstructive pulmonary disease]. 1602 95

Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory illnesses characterized by chronic inflammation of the airways. The characterization of induced or spontaneously produced sputum is a useful technique to assess airway inflammation. In the present study, we compared the concentrations of CCL2, CCL11, CXCL8, and tumor necrosis factor-alpha (TNF-alpha) in plasma and induced sputum of patients with severe asthma or COPD and correlated the levels of these mediators with inflammatory cells in sputum. Asthmatic patients had elevated levels of eosinophils (40.1 +/- 6.24%) in sputum whereas neutrophils (63.3 +/- 4.66%) predominated in COPD patients. The levels of the chemokine CCL11 were markedly increased in sputum (708.7 +/- 330.7 pg/ml) and plasma (716.6 +/- 162.2 pg/ml) of asthmatic patients and correlated with the percentage of eosinophils in induced sputum. The concentrations of CXCL8 (817.0 +/- 105.2 pg/ml) and TNF-alpha (308.8 +/- 96.1 pg/ml) were higher in sputum of COPD patients and correlated with the percentage of neutrophils in induced sputum. There was also an increase in the concentrations of CXCL8 (43.2 +/- 6.8 pg/ml) in sputum of asthmatic patients. These results validate that sputum is a suitable method to assess chemokines and cytokines associated with asthma and COPD. Moreover, the mechanisms involved in the synthesis of CCL11 and CXCL8/TNF-alpha would be helpful to better understand the inflammatory profile associated with asthma and COPD, respectively.
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PMID:Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation. 1613 19

Breast-feeding decreases maternal breast cancer risk. Breast-fed infants have fewer infections and inflammatory-allergic diseases. We recently found inducible antimicrobial and immunomodulatory protein human beta3-defensin 2 (HBD-2) in significant amounts in human milk. We investigated if HBD-2 could contribute to benefits of breast-feeding for the mother and the child by immunomodulating effects on breast and gut epithelial cells. Human CaCo-2 colon and MCF-7 breast cell lines were cultured for 16-48 hours in RPMI 1640 5% fetal calf serum with and without HBD-2 at 0.1, 0.5, and 1.0 microg/mL. RNA was extracted and reverse-transcription polymerase chain reaction (RT-PCR) and gel electrophoresis for toll-like receptor pathway members, antimicrobial peptides, and cytokines/receptors was performed. Primers were designed with www.ncbi.nlm.nih.gov and www.broad. mit.edu/cgibin/primer/primer3 www.cgi. Based on RT-PCR results, cells were stained by immunohistochemistry using anti-toll-like receptor (TLR)-7 and anti-LL37 antibodies and DAKO EnVision Plus kits. Supernatants were analyzed for interleukin (IL)-8 and liver and activation-regulated chemokine (LARC) using enzyme-linked immunosorbent assay. In CaCo-2, messenger RNA (mRNA) for TLR-7, IL-1R-associated kinase, alpha-defensins (human neutrophil peptides 1-3), and IL-8 were down-regulated; cathelicidin/LL37 and NFkappaBp65 were up-regulated. LARC mRNA and protein were detected after 48 hours. TLR-7 protein, LARC, and IL-8 decreased with HBD-2; LL-37 protein greatly increased. In MCF-7, mRNA for LL37, inhibitor of kappaBalpha, NFkappaBp65, Tollip, MyD88, IL-1R-associated kinase, and TLR-7 were up-regulated. LARC mRNA was turned off. TLR-7 protein was induced. LARC was not detected. IL-8 was barely detectable with or without HBD-2. beta-Defensins 1 and 2; alpha-defensins 5 and 6; TLRs 1, 2, 3, 4, 5, 6, 8, 9, and 10; nucleotide binding oligomerization domain protein-2, and CCR6 mRNA were unaffected. HBD-2 profoundly alters the innate immune response of breast and intestinal epithelial cells.
Allergy Asthma Proc
PMID:Modulation of toll-like receptor 7 and LL-37 expression in colon and breast epithelial cells by human beta-defensin-2. 1627 Jul 24

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation. However, because patients with COPD and certain patients with asthma show little or no therapeutic benefit from existing corticosteroid therapies, there is an urgent need for novel anti-inflammatory strategies. The transcription factor nuclear factor-kappaB (NF-kappaB) is central to inflammation and is necessary for the expression of numerous inflammatory genes. Proinflammatory cytokines, including interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha, activate the IkappaB kinase complex (IKK) to promote the degradation of inhibitory IkappaB proteins and activate NF-kappaB. This pathway and, in particular, the main IkappaB kinase, IKK2, are now considered prime targets for novel anti-inflammatory drugs. Therefore, we have used adenoviral overexpression to demonstrate NF-kappaB and IKK2 dependence of key inflammatory genes, including intercellular adhesion molecule (ICAM)-1, cyclooxygenase-2, IL-6, IL-8, granulocyte macrophage-colony-stimulating factor (GM-CSF), regulated on activation normal T cell expressed and secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), growth-regulated oncogene-alpha (GROalpha), neutrophil-activating protein-2 (NAP-2), and epithelial neutrophil activating peptide 78 (ENA-78) in primary human airways smooth muscle cells. Because this cell type is central to the pathogenesis of airway inflammatory diseases, these data predict a beneficial effect of IKK2 inhibition. These validated outputs were therefore used to evaluate the novel IKK inhibitors N-(6-chloro-9H-beta-carbolin-8-yl) nicotinamide (PS-1145) and N-(6-chloro-7-methoxy-9H-beta-carbolin-8-yl)-2-methyl-nicotinamide (ML120B) on IL-1beta and TNFalpha-induced expression, and this was compared with the corticosteroid dexamethasone. As observed above, ICAM-1, IL-6, IL-8, GM-CSF, RANTES, MCP-1, GROalpha, NAP-2, and ENA-78 expression was reduced by the IKK inhibitors. Furthermore, this inhibition was either as effective, or for ICAM-1, MCP-1, GROalpha, and NAP-2, more effective, than a maximally effective concentration of dexamethasone. We therefore suggest that IKK inhibitors may be of considerable benefit in inflammatory airways diseases, particularly in COPD or severe asthma, in which corticosteroids are ineffective.
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PMID:Validation of the anti-inflammatory properties of small-molecule IkappaB Kinase (IKK)-2 inhibitors by comparison with adenoviral-mediated delivery of dominant-negative IKK1 and IKK2 in human airways smooth muscle. 1668 66

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation and major structural lung tissue changes including increased extracellular matrix (ECM) deposition. Inhaled corticosteroids and long-acting beta(2)-agonists (LABA) are the basic treatment for both diseases, but their effect on airway remodeling remains unclear. In this study, we investigated the effect of corticosteroids and LABA, alone or in combination, on total ECM and collagen deposition, gene expression, cell proliferation, and IL-6, IL-8, and TGF-beta(1) levels by primary human lung fibroblasts. In our model, fibroblasts in 0.3% albumin represented a non-inflammatory condition and stimulation with 5% FCS and/or TGF-beta(1) mimicked an inflammatory environment with activation of tissue repair. FCS (5%) increased total ECM, collagen deposition, cell proliferation, and IL-6, IL-8, and TGF-beta(1) levels. In 0.3% albumin, corticosteroids reduced total ECM and collagen deposition, involving the glucocorticoid receptor (GR) and downregulation of collagen, heat shock protein 47 (Hsp47), and Fli1 mRNA expression. In 5% FCS, corticosteroids increased ECM deposition, involving upregulation of COL4A1 and CTGF mRNA expression. LABA reduced total ECM and collagen deposition under all conditions partly via the beta(2)-adrenergic receptor. In combination, the drugs had an additive effect in the presence or absence of TGF-beta(1) further decreasing ECM deposition in 0.3% albumin whereas counteracting each other in 5% FCS. These data suggest that the effect of corticosteroids, but not of LABA, on ECM deposition by fibroblasts is altered by serum. These findings imply that as soon as airway inflammation is resolved, long-term treatment with combined drugs may beneficially reduce pathological tissue remodeling.
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PMID:Opposite effect of corticosteroids and long-acting beta(2)-agonists on serum- and TGF-beta(1)-induced extracellular matrix deposition by primary human lung fibroblasts. 1701 7

Asthma is a chronic inflammatory disorder of the airways; therefore, establishing a simple monitoring system of airway inflammation would be useful for asthma management. Exhaled breath condensate (EBC), which is formed by breathing with a cooling system, is a non-invasive biomarker for airway inflammation. We have shown that nine kinds of molecules; namely, IL-4, IL-8, IL-17, TNF-alpha, RANTES, IP-10, TGF-beta, MIP-1alpha, and MIP-1beta, are over-expressed in asthmatic airways compared with those of healthy subjects using EBC analysis. In addition, the levels of some over-expressed molecules and lung physiologic indices are correlated. RANTES expression was significantly correlated with the degree of airflow limitation. Further, both TNF-alpha and TGF-beta values were significantly correlated with the degree of airway responsiveness and variability of peak expiratory flow. Additionally, the comparison of molecular properties between EBC and saliva indicated that saliva contamination is not a dominant contributor to the assessment of inflammatory molecules in EBC. Analysis of inflammatory molecules using EBC should be useful for monitoring the asthmatic airway condition, and might be a promising approach to assess the efficacy of pharmacologic interventions and to investigate the pathophysiology of asthma.
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PMID:[The utility of exhaled breath condensate analysis for asthma management]. 1751 Dec 69

Intermittent allergic rhinitis and common cold constitute frequent conditions and show similar clinical symptoms. The purpose of this study was to investigate the pattern of cytokines in the nasal fluid of patients with acute symptoms caused by allergic and viral rhinitis. Nasal secretions were analyzed by immunosorbent assay techniques using a cytokine panel assay and routine ELISA. Allergic patients had significantly higher levels of eosinophil cationic protein (ECP), interleukin (IL)-5, and tryptase. Significantly elevated concentrations of proinflammatory cytokines (IL-1b, IL-6, IL-7, IL-17, interferon [IFN] gamma, and tumor necrosis factor [TNF]-alpha) as well as chemokines for cellular infiltration (IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1beta), factors for cellular proliferation (granulocyte colony-stimulating factor [G-CSF] and granulocyte macrophage colony-stimulating factor [GM-CSF]), and elastase were found in viral rhinitis. IL-10 was only detectable in viral rhinitis. IL-4 was significantly higher in patients with viral rhinitis than allergic rhinitis, and IL-5 was significantly elevated in viral rhinitis compared with controls. In viral-triggered rhinitis, we detected a predominantly Th1-type cytokine pattern with potent proinflammatory mediators. Factors reflecting a neutrophil and eosinophil immune response, due to IL-5, IL-8, GM-CSF, ECP, and elastase were shown. Nasal secretions of patients with allergic rhinitis showed highest concentrations of tryptase, IL-5, and ECP, reflecting a mast cell and eosinophil immune response. Nasal secretion levels of IL-4 did not show highest levels in allergic rhinitis but did in viral rhinitis. IL-4 also may play a role in limiting inflammatory processes by inhibiting the production of inflammatory cytokines.
Allergy Asthma Proc
PMID:Mediators and cytokines in allergic and viral-triggered rhinitis. 1788 11

Chronic cough can be a complicated and frustrating diagnostic dilemma. The aim of this study was to identify the possible causes of chronic nonspecific cough in seemingly healthy children using fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). Eighteen children responded to criteria of selection for chronic cough. The average age was 5.8 years (range, 1.7-10.7 years) and BAL findings were compared with those of 16 nonatopic controls. Children with chronic cough had an increased percentage of BAL neutrophils in comparison with the control group (p = 0.098). Using a BAL neutrophil percent cutoff of 17%, 6 children had high BAL neutrophils (HBNs; median, 77%; range, 27-96%) and 12 children had normal BAL neutrophils (NBNs; median, 3%; range, 0-13%). In the HBN group, FOB showed endoscopic abnormalities in four patients, BAL culture was positive in three patients, and chest x-ray (CXRs) showed minimal densities in four. The IL-8 levels showed a significant increase with respect to the NBN group (p = 0.005). The combination of endoscopic anomalies, BAL culture, BAL IL-8 levels, and minor CXR changes can support the diagnosis of subclincal infection in seemingly healthy children with chronic nonspecific cough and HBN.
Allergy Asthma Proc
PMID:Investigation of children with chronic nonspecific cough: any clinical benefit of bronchoscopy and bronchoalveolar lavage? 1788 15

The aim of this study was to explore possible interactions between a glucocorticosteroid (budesonide) and a long-acting beta(2)-agonist (formoterol) on pro-inflammatory cytokine release. Primary bronchial epithelial cells (PBEC) were stimulated with organic dust and incubated with budesonide, formoterol, and the combination of both drugs. Interleukin (IL)-6 and -8 in the supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). Formoterol increased the IL-6 release but did not influence the IL-8 release. Budesonide attenuated the IL-6 and IL-8 release, an inhibiting effect that was sustained, but not reinforced, by formoterol.
J Asthma 2008 Apr
PMID:Effect of budesonide and formoterol on IL-6 and IL-8 release from primary bronchial epithelial cells. 1841 26

Exercise-induced bronchospasm (EIB) occurs in athletes with and without asthma. Studies have suggested an inflammatory basis for EIB in asthmatics; however whether inflammation plays a similar role in EIB in athletes without asthma remains unclear. Our objective was to determine whether there is evidence of an inflammatory basis for exercise-induced bronchospasm occurring in non-asthmatic athletes. Ninety-six athletes without asthma from varsity college teams underwent eucapnic voluntary hyperventilation testing. Sputum was induced from subjects with hypertonic saline inhalation post-eucapnic voluntary hyperventilation testing and was analyzed with enzyme-linked immunosorbent assays for IL-5, IL-8, IL-13, cysteinyl-leukotrienes, prostaglandin E2, histamine, leukotriene B4, and thromboxane B2. In addition, inflammatory (neutrophils, lymphocytes, eosinophils, and macrophages) and epithelial cell counts in sputum were recorded. Multivariate regression modeling showed a significant correlation between concentrations of select inflammatory mediators after eucapnic voluntary hyperventilation testing and severity of EIB. Means of the log-transformed concentrations of inflammatory mediators in EIB-positive athletes were significantly higher post-eucapnic voluntary hyperventilation than in EIB-negative athletes. Similar findings were not demonstrated with inflammatory cells. Concentrations of inflammatory mediators are higher in EIB-positive athletes than in EIB-negative athletes without asthma after eucapnic voluntary hyperventilation testing. The severity of EIB in our cohort also is significantly correlated with increased concentrations of select inflammatory mediators suggesting a potential inflammatory basis for EIB in athletes without asthma.
J Asthma 2008 Jun
PMID:Airway inflammation in exercise-induced bronchospasm occurring in athletes without asthma. 1856 28

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