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)

Inflammation of the central airways is a prominent feature in subjects with chronic bronchitis. The pathology of chronic bronchitis includes an inflammatory mononuclear cell infiltrate in the airway wall and a neutrophil influx into the airway lumen. The molecular events that produce the inflammation and its pathogenetic role in causing mucus hypersecretion are beginning to be elucidated. The inflammatory cell recruitment to the airways likely involves chemotactic agents derived not only from tissue fluid and invading microbes but also generated by the diseased bronchial epithelium. For example, bronchial epithelial cells synthesize interleukin (IL-8), a potent chemoattractant and activator of neutrophils and lymphocytes. Adhesion of infiltrating leukocytes to resident parenchymal cells in the bronchi and to extracellular matrix also is crucial for the development of airway inflammation. The resultant inflammation likely plays a direct role in the clinical features of the disorder. There is growing evidence incriminating neutrophil and lymphocytes constituents in the initiation and maintenance of cough and mucus expectoration that occurs in subjects with chronic bronchitis.
 ...
PMID:Pathogenesis of chronic bronchitis. 797 68

Cultured human bronchial epithelial cells (HBEC) produce both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 8 (IL-8). The influence of cefodizime (CAS 69739-16-8), a new broad spectrum cephalosporin with immunostimulatory effects, and ceftriaxone on the production of GM-CSF and IL-8 in HBEC primary cultures was investigated. HBEC were isolated from biopsy specimens obtained during fibreoptic bronchoscopy in 12 patients (most frequent diagnosis: chronic bronchitis). Confluent monolayers of HBEC cultured on collagen were incubated for 24 h in a medium without study drugs (spontaneous production) or containing cefodizime or ceftriaxone at the clinically relevant concentrations of 1, 10 and 100 mg/l, with or without tumor necrosis factor alpha (TNF alpha, 100 U/ml). GM-CSF and IL-8 were measured in supernatant by ELISA technique. TNF alpha alone led to a significant (p < 0.005) increase in both GM-CSF and IL-8 production. Cefodizime induced a significant (p < 0.05), dose-dependent increase in GM-CSF release. No additive effect of cefodizime with TNF alpha was observed. Cefodizime did not affect IL-8 production and ceftriaxone had no influence on cytokine production. This is the first report of a stimulatory effect of a beta-lactam antibiotic on cytokine production by epithelial cells. GM-CSF production by epithelial cells is an important immunological step for neutrophil and monocyte recruitment and cell priming during lung defence. Previous studies with cefodizime in immunodepressed subjects have shown activation of phagocytosis and phagocytosis-related functions in non-lung phagocytes. An indirect mechanism of action, similar to that indicated by our results, may have been responsible for these stimulatory effects.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Antibiotics and production of granulocyte-macrophage colony-stimulating factor by human bronchial epithelial cells in vitro. A comparison of cefodizime and ceftriaxone. 801 Oct 12

Although macrolide antibiotics have now been widely used in the treatment of chronic airway infections including diffuse panbronchiolitis and chronic bronchitis, the mechanism of the efficacy remains uncertain. Because the increased mucus glycoprotein secretion from airway goblet cells may play a significant role in the development of such diseases, to determine the effects of macrolides on airway goblet cell secretion, we studied guinea pig airways by a semiquantitative morphometric method. The goblet cell secretion was assessed in histological sections of the trachea and main bronchi stained with Alcian blue and PAS by determining mucus score, which is inversely related to the magnitude of mucus discharge. Intravenous IL-8 decreased mucus score in a dose-dependent manner and increased the number of neutrophils present in bronchoalveolar lavage fluid. Oral administration of clarithromycin at a daily dose of 1-10 mg/day for 2 weeks dose-dependently inhibited IL-8 (5 mg/ kg)-induced decrease in mucus score, with the maximal inhibition being 54 +/- 11% (p < 0.001) in the trachea and 48 +/- 8% (p < 0.01) in the main bronchi. This effect was accompanied by the inhibition of neutrophil accumulation into bronchoalveolar lavage fluid. Erythromycin produced similar inhibitory effects on IL-8-induced goblet cell secretion and neutrophil accumulation, whereas amoxicillin and cefaclor had no effect. These results suggest that macrolides protect against goblet cell hypersecretion probably through an inhibition of recruitment of neutrophils into the airway mucosa.
 ...
PMID:[Effect of macrolide antibiotics on airway goblet hypersecretion in guinea pigs]. 874 8

This review focuses on bacterial induction and release of inflammatory cytokines and adhesion molecules by human bronchial epithelial cells, with special reference to Haemophilus influenzae, a pathogen commonly associated with chronic bronchitis. Studies investigating the mechanisms underlying bacterial colonization of the airways and bacterial-induced chronic airway inflammation have suggested that these are likely to involve localization of bacteria to the site(s) of infection in the respiratory tract and induction of a local airway inflammation resulting in the initiation of epithelial damage. We have hypothesized that the gross airway epithelial damage observed in chronic infective lung disease is an indirect consequence of proteolytic enzymes and toxic oxygen radicals generated by large numbers of neutrophils infiltrating the airways. Furthermore, the infiltration and activation of the neutrophils is a consequence of increased release of proinflammatory mediators from the host respiratory epithelium, induced by bacterial products, such as endotoxin. This hypothesis is based on studies which have demonstrated that the concentrations of circulating cytokines, such as interleukin (IL)-8 and tumour necrosis factor-alpha (TNF-alpha), which have profound effects on neutrophil activity, are increased in endotoxaemia and that airway epithelial cells are a rich source of these cytokines. Support for this hypothesis is provided by studies of cultured human bronchial epithelial cells incubated either in the absence or presence of purified endotoxin preparations from nontypable and type b H. influenzae strains which have demonstrated that these endotoxins lead to significantly increased expression and/or release of proinflammatory mediators, including IL-6, IL-8, TNF-alpha and intercellular adhesion molecule-1 (ICAM-1). Treatment of the cells with steroids can downregulate the expression and/or release of these inflammatory mediators. Additionally, these studies have demonstrated that culture medium collected from endotoxin-treated cultures, 24 h after treatment, significantly increases neutrophil chemotaxis and adhesion to human endothelial cells in vitro.
 ...
PMID:Bacterial-induced release of inflammatory mediators by bronchial epithelial cells. 888 Jan 12

The present study was aimed at elucidating the role of inflammatory cells in the pathogenesis of the chronic inflammatory changes in the bronchioles of patients with diffuse panbronchiolitis (DPB) and at determining the mechanism for the clinical efficacy of erythromycin (EM) therapy for these patients. For this purpose, neutrophil percentages, neutrophil chemotactic activity (NCA), IL-8 and TNF-alpha in the bronchoalveolar lavage fluid (BALF) were measured in 9 patients with DPB. Significantly higher neutrophil percentages, NCA and IL-8 concentrations were demonstrated in the BALF from DPB patients than from chronic bronchitis (CB) patients or healthy control subjects. The levels of these indicators of chronic inflammation in the BALF from DPB patients were significantly decreased after EM therapy. TNF-alpha was elevated in the BALF from both DPB- and CB-patients and was not decreased by treatment of the DPB patients with EM. From the above results, it can be concluded that IL-8, not TNF-alpha, is the major chemoattractant for neutrophils and that the inhibition of IL-8 production by EM induces the subsequent depression of neutrophil accumulation in the peripheral airways, and consequently, prevents the peripheral airway tissue damage due to accumulated and activated neutrophils.
 ...
PMID:Neutrophil chemotactic activity in bronchoalveolar lavage fluid recovered from patients with diffuse panbronchiolitis. 902 97

Cigarette smoking causes the development of chronic bronchitis and chronic obstructive pulmonary disease. We hypothesized that exposure to cigarette smoke might initiate release of inflammatory mediators by bronchial epithelial cells. To evaluate this, the effect of cigarette smoke extract (CSE) on IL-8 release from cultured human bronchial epithelial cells was examined. CSE augmented IL-8 release from bronchial epithelial cells in a concentration- and time-dependent manner. Most of the augmenting activity of CSE on IL-8 release from bronchial epithelial cells was lost after volatilization or lyophilization treatment. Two major volatile factors in cigarette smoke, acrolein and acetaldehyde, augmented IL-8 release. Four cell strains were tested and showed increased IL-8 release in response to CSE. In addition, bronchoalveolar lavage was performed on 11 nonsmokers and 12 smokers. IL-8 concentration was greater in the proximal, bronchial samples than in distal, alveolar samples, and IL-8 in BAL from smokers was higher than in BAL from nonsmokers. There was a significant correlation between IL-8 concentration and neutrophil count in bronchial samples of BAL fluid. These data support the hypothesis that exposure to cigarette smoke may induce bronchial epithelial cells to release IL-8 and that this may contribute to airway inflammation in smokers.
 ...
PMID:Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells. 915 90

Chemical exposure may result in respiratory conditions such as chronic bronchitis, bronchial hyperresponsiveness, and chronic airway obstruction. Clinical studies have shown that during the course of disease, cytokine networks are changed. In order to study the relationship between blood cytokines and respiratory symptoms in an occupational setting, we investigated 106 chemical workers during a routine yearly medical examination in 1995. Lung function was measured with flow volume curves and impedance using the forced oscillation technique (FOT). Smoking-status and respiratory symptoms were determined by questionnaires. Cytokines were selected on biological plausibility and measured both in a whole blood assay (TNF-alpha, IL-8) and in serum (IL-4, IL-5, IL-6, IFN-gamma). The hypothesis is that blood levels of TNF-alpha and IL-8 are increased in bronchitis, while serum levels of IL4, IL-5 are increased and IFN-gamma is decreased in asthmatic workers. Spontaneous IL-8 release was significantly higher in workers with bronchitis (P < 0.05) or chronic bronchitis (P < 0.01) compared to workers without those respiratory symptoms, also after correction for age, pack-years, and blood lymphocyte numbers or compared to a matched control group. No correlation was present between specific cytokines and asthmatic symptoms. These data suggest that blood IL-8 may be considered as a useful marker for bronchitis.
 ...
PMID:Blood interleukin-8 production is increased in chemical workers with bronchitic symptoms. 935 25

Nonencapsulated Haemophilus influenzae strains isolated from patients with chronic bronchitis can be divided into those that persist in the lower respiratory tract and those that do not. We tested the hypothesis that persisting and nonpersisting strains differ in the extent to which they activate epithelial cells to produce two potent inflammatory mediators, interleukin (IL)-6 and IL-8. A suspension of 10(7) and 10(8) colony forming units (cfu) x mL(-1) of H. influenzae, persisting and nonpersisting, induced a dose- and time-dependent production of IL-6 and IL-8 by the human pulmonary mucoepidermoid carcinoma-derived cell line H292, but levels of IL-6 were lower after exposure to persisting H. influenzae (p<0.05). IL-8 production showed a similar trend (p<0.02; analysis of variance). H. influenzae bacteria that adhered to H292 cells were equally distributed over persisting and nonpersisting isolates and induced IL-6 and IL-8 levels similar to their nonadhering counterparts. The difference between persisting and nonpersisting H. influenzae was not due to cytotoxic, antimetabolic or antiproliferative effects on H292 cells. Furthermore, pre-exposure of cells to persisting and nonpersisting isolates did not block subsequent IL-1beta-induced IL-6 production. We conclude that persisting clinical isolates induce less interleukin-6 and interleukin-8 in H292 cells than nonpersisting isolates, probably because they excrete lower amounts of a stimulus of H292 cells. The stimulus is heat stable, hydrophilic and nonproteinous and probably not lipopolysaccharide alone. These findings support the suggestion that some strains of Haemophilus influenzae that persist in the airways of patients, may do so because they induce only a weak inflammatory response.
 ...
PMID:Persisting Haemophilus influenzae strains induce lower levels of interleukin-6 and interleukin-8 in H292 lung epithelial cells than nonpersisting strains. 938 60

Neutrophils isolated from patients with chronic bronchitis and emphysema have been shown to have enhanced responses to formyl peptides when assessed in vitro compared to age, sex matched controls. It is currently unclear whether the observed differences are due to a 'priming' effect by a second agent in vivo, or whether this is a primary difference in the neutrophils. We have studied the effects of interleukin-8, which is thought to be one of the major pro-inflammatory cytokines in chronic lung disease and granulocyte macrophage colony stimulating factor (GMCSF), in order to assess their effects on neutrophil chemotaxis and connective tissue degradation. In addition, we have assessed the effect of preincubation of these agents with neutrophils for 30 min followed by stimulation with F-Met-Leu-Phe (FMLP) to investigate any possible 'priming' effect that may be relevant to our clinical data. We report suppression of neutrophil chemotaxis to FMLP following incubation of the neutrophils with both IL-8 and GMCSF. However, we have observed an additive effect of IL-8 and FMLP for neutrophil degranulation leading to fibronectin degradation. The results suggest that IL-8 does not 'prime' neutrophils for subsequent FMLP stimulation as observed in vivo. Although the results for GMCSF were similar for the chemotactic response, the agent also had a synergistic effect on connective tissue degradation. However, it is concluded that neither agent could explain the enhanced neutrophil responses seen in our patients.
 ...
PMID:The effect of interleukin-8 and granulocyte macrophage colony stimulating factor on the response of neutrophils to formyl methionyl leucyl phenylalanine. 968 20

Macrolide antibiotics are known to be effective for the treatment of chronic inflammatory airway diseases including diffuse panbronchiolitis, chronic bronchitis, and bronchial asthma. Other than having antimicrobial activities, macrolides have antiinflammatory effects, such as the inhibition of cytokine production. In the present study we investigated the effects of clarithromycin (CAM) on interleukin (IL)-8 gene expression and protein levels, using the human bronchial epithelial cell line BET-1A. Northern blot analyses showed that CAM inhibited tumor necrosis factor (TNF)-alpha-induced IL-8 gene expression in a dose- and incubation time-dependent manner. The half-life of IL-8 messenger RNA transcripts in TNF-alpha-treated BET-1A cells did not change with CAM. Transfection studies with BET-1A cells, using fusion genes composed of the 5'-flanking sequences of the IL-8 gene and a luciferase reporter gene, demonstrated potent promoter activity in a 174-bp segment (-130 to +44 bp relative to the transcription start site). This segment includes activator protein (AP)-1 and nuclear factor (NF)-kappaB-like sites, and exhibited its strongest response to TNF-alpha. TNF-alpha-induced promoter activity in this segment showed a significant repression by CAM. However, a 156-bp segment (-112 to +44 bp) that does not include an AP-1 site but includes an NF-kappaB-like site did not show a significant repression of TNF-alpha-induced promoter activity by CAM. Mutation of the AP-1 binding site abrogated the suppression by CAM of TNF-alpha-induced enhancement of luciferase activity. In accord with promoter analyses, an electrophoretic mobility shift assay showed that CAM repressed AP-1 binding in TNF-alpha-treated BET-1A cells; however, TNF-alpha induced both AP-1 and NF-kappaB binding activities in BET-1A cells. These data suggest that macrolides such as CAM repress IL-8 gene transcription mainly via the AP-1 binding site in human bronchial epithelial cells. Our findings provide a novel mechanism for the antiinflammatory function of macrolides, implicating a target for the development of new drugs for treating chronic airway inflammation.
 ...
PMID:Interleukin-8 gene repression by clarithromycin is mediated by the activator protein-1 binding site in human bronchial epithelial cells. 1061 65


1 2 3 4 Next >>