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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of dexamethasone, pentoxifylline, and MAb against endotoxin (HA-1A) on the release of various proinflammatory mediators, i.e. tumor necrosis factor-alpha (TNF), IL-1 beta, IL-8, and prostaglandin 2, by human leukocytes during stimulation with Haemophilus influenzae type B were studied. The results show that only monocytes, and thus neither lymphocytes nor granulocytes, release these mediators in response to H. influenzae. Dexamethasone inhibited the release of all of these mediators, whereas pentoxifylline only inhibited the release of TNF. HA-1A only reduced the release of IL-8 from adherent monocytes significantly and had no significant effect on the release of TNF, IL-1 beta, and prostaglandin E2. In whole blood, no significant effect of HA-1A on the release of TNF, IL-1 beta, IL-8, and prostaglandin E2 was found. In summary, the results of this study demonstrate that dexamethasone is the most potent inhibitor of the release of proinflammatory mediators by monocytes induced by H. influenzae type B.
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PMID:In vitro effect of dexamethasone, pentoxifylline, and anti-endotoxin monoclonal antibody on the release of proinflammatory mediators by human leukocytes stimulated with Haemophilus influenzae type B. 793 25

Respiratory infections in Japan have rapidly changed, because pathogenesis has also changed by the increase of compromised hosts and aged people with the development of chemotherapeutic agents and another medical progresses. Various respiratory infections have been accumulated in our clinical department and clinical investigations were done for these diseases during almost 20 years. Firstly, pneumonias in adult T cell leukemia have been very severe and these diseases have occurred with load from pathogenic orophayngeal bacteria to lower respiratory airway. With another clinical studies, these pathogenesis which firstly pathogenic bacteria attach to orophayngeal epithelial cells and would move to lower respiratory airway to infect were given very clear evidences especially for Branhamella and Pneumococcus infections with chronic respiratory infections. The exact clearance of pathogenic orophayngeal bacteria using povidon iode solution was very useful for prevention of these acute or chronic respiratory infections. Although acute bronchitis is very popular, the secondary bacterial pathogens remained to be unknown, in the world. We showed that H. influenzae, S.pneumoniae and B.catarrhalis were common major pathogens as the secondary invading bacteria of acute bronchitis in Japan, Thailand and Bangladesh. Recently, the pathogenesis of severe chronic respiratory infections such as diffuse panbronchiolitis is focused after the development of erythromycin therapy. We gave some evidences of macrolides effectiveness which these drugs inhibited IL-8 production. We described the importance of inflammatory cell classification in sputa or bronchial secretions for deep understanding of inflammatory situation in broncho-bronchiolar airway.(ABSTRACT TRUNCATED)
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PMID:[Respiratory infections--pathogenesis of acute and chronic infections]. 883 Nov 94

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.
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PMID:Bacterial-induced release of inflammatory mediators by bronchial epithelial cells. 888 Jan 12

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.
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PMID:Persisting Haemophilus influenzae strains induce lower levels of interleukin-6 and interleukin-8 in H292 lung epithelial cells than nonpersisting strains. 938 60

We have previously shown that tonsil tissue both from children with tonsillar hypertrophy and recurrent tonsillitis is colonized and invaded by Haemophilus influenzae and Streptococcus pyogenes group A. In order to evaluate if these bacteria are involved in the immunopathogenesis of these two conditions, tonsillar cells from both groups were stimulated in vitro with intact, heat-inactivated H. influenzae or S. pyogenes A. The immunoreactivity was evaluated by assessing the induction of cytokine production (IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, IL-8, IL-2, IFN-gamma, IL-4, TNF-beta and IL-10), which was detected at the single-cell level. All cytokines studied except IL-4 were induced in both groups after stimulation with H. influenzae or S. pyogenes A. The dominating cytokines were IL-1 beta, IFN-gamma and TNF-beta. No major differences in the cytokine pattern or number of cytokine-producing cells were noticed between the two patient cohorts after H. influenzae stimulation. Activation by S. pyogenes A bacteria gave rise to higher frequencies of IFN-gamma- and TNF-beta-synthesizing cells in the recurrent tonsillitis group. The incidence of CD4-, CD8-positive T cells and CD40-positive B cells was comparable between the two groups while the MAC-387-positive macrophages were significantly higher in the recurrent tonsillitis groups. In conclusion, a Th1 type of cytokine response was found in both groups following stimulation with H. influenzae or S. pyogenes A.
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PMID:Haemophilus influenzae and Streptococcus pyogenes group A challenge induce a Th1 type of cytokine response in cells obtained from tonsillar hypertrophy and recurrent tonsillitis. 951 80

The aim of this study was to analyse the in vitro response of human peripheral blood mononuclear cells to stimulation with killed Haemophilus influenzae strains of different capsular types, isolation sites and from cases with different forms of infections. The mean stimulatory index using 10(6) bacteria/well was 10, and 80 when 10(8) bacteria/well were used for stimulation. The mean+/-SD level was 13+/-4 ng/ml for interleukin (IL)-1beta, 128+/-73 ng/ml for IL-6, 203+/-122 ng/ml for IL-8, 3160+/-1220 pg/ml for IL-10, 29+/-40 pg/ml for IL-12, 2800+/-1790 pg/ml for tumour necrosis factor (TNF)-alpha and 4+/-7 ng/ml for interferon (IFN)-gamma, when stimulating cells with the lower dose of 10(6) bacteria/well. Using the higher bacterial dose, the levels of IL-1beta, TNF-alpha and IL-12 remained similar, whereas the IL-6, IL-8 and IL-10 levels were significantly lower, and IFN-gamma levels were significantly higher. Strains isolated from the bronchial tree induced significantly higher levels of IFN-gamma and significantly lower levels of IL-6, IL-8 and IL-10 than strains from other isolation sites. In conclusion, H. influenzae generated phagocyte-activating cytokines and an IL-10/IL-12 ratio that was 1090 times that described previously for Streptococcus pneumoniae.
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PMID:Induction of phagocyte-stimulating cytokines by in vitro stimulation of human peripheral blood mononuclear cells with Haemophilus influenzae. 1021 68

To characterize the local response in acute otitis media, courses of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)alpha in middle ear fluid (MEF) of the guinea pig otitis media model induced by nonviable Haemophilus influenzae were investigated with enzyme-linked immunosorbent assay (ELISA) kits. The IL-1beta concentration in H. influenzae-inoculated ears peaked 24 hours after inoculation. The IL-8 concentration was significantly higher in H. influenzae-inoculated ears than in controls 48 and 96 hours after inoculation. The TNF-alpha concentration in H. influenzae-inoculated ears had an initial peak 6 hours after inoculation and had significant late increases 48 and 96 hours after inoculation. The results suggest that IL-1beta and TNF-alpha were produced by middle ear mucosa in the early stage of the experiment by stimulation of bacterial inoculation, which caused subsequent inflammatory cell accumulation, and that IL-8 and TNF-alpha were produced in the late stage by accumulating inflammatory cells.
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PMID:Course of IL-1beta, IL-6, IL-8, and TNF-alpha in the middle ear fluid of the guinea pig otitis media model induced by nonviable Haemophilus influenzae. 1037 23

Epithelial cells interact directly with bacteria in the environment and play a critical role in airway defense against microbial pathogens. In this study, we examined the response of respiratory epithelial cells to infection with nontypable Haemophilus influenzae. Using an in vitro cell culture model, we found that epithelial cell monolayers released significant quantities of IL-8 and expressed increased levels of ICAM-1 mRNA and surface protein in response to H. influenzae. In contrast, levels of IL-1beta, TNF-alpha, and MHC class I were not significantly affected, suggesting preferential activation of a specific subset of epithelial genes directed toward defense against bacteria. Induction of ICAM-1 required direct bacterial interaction with the epithelial cell surface and was not reproduced by purified H. influenzae lipooligosaccharide. Consistent with a functional role for this response, induction of ICAM-1 by H. influenzae mediated increased neutrophil adherence to the epithelial cell surface. Furthermore, in an in vivo murine model of airway infection with H. influenzae, increased epithelial cell ICAM-1 expression coincided with increased chemokine levels and neutrophil recruitment in the airway. These results indicate that ICAM-1 expression on human respiratory epithelial cells is induced by epithelial cell interaction with H. influenzae and suggest that an ICAM-1-dependent mechanism can mediate neutrophil adherence to these cells independent of inflammatory mediator release by other cell types. Direct induction of specific epithelial cell genes (such as ICAM-1 and IL-8) by bacterial infection may allow for rapid and efficient innate defense in the airway.
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PMID:Haemophilus influenzae stimulates ICAM-1 expression on respiratory epithelial cells. 1075 14

Nonencapsulated Haemophilus influenzae often causes chronic infections of the lower respiratory tract in both nonobstructive and obstructive chronic bronchitis. We assessed airway inflammation in clinically stable, chronically H. influenzae-infected patients with nonobstructive (CB-HI, n = 10) and in patients with obstructive chronic bronchitis (COPD-HI, n = 10) by analyses of the sol phase of spontaneously expectorated sputum (SSP). As compared with the CB-HI group, the COPD-HI group had significantly higher (p < 0.05) levels of myeloperoxidase (MPO) and tumor necrosis factor (TNF)-alpha in their SSP, whereas the degree of plasma protein leakage (SSP-to-serum ratio of plasma proteins) and the levels of interleukin (IL)-8, secretory IgA, and lactoferrin were similar in the two groups. These findings point to differences in pathophysiology in CB-HI and COPD-HI. The high level of TNF-alpha in the SSP of COPD-HI patients is in accord with the proposed role of TNF-alpha in the development of airway obstruction in COPD patients. In apparent contradiction, low levels of TNF-alpha were found in the SSP of noninfected but otherwise similar COPD patients (n = 9). This finding, however, does not exclude an exaggerated TNF-alpha response to infection or another stimulus in the airways of COPD patients. The SSP levels of MPO and IL-8, and the degree of plasma protein leakage in the COPD-HI group, were retrospectively compared with and found significantly higher than those of noninfected COPD patients, suggesting a more marked inflammatory response in COPD-HI. Whether this reflects a direct cause-and-effect relationship should be addressed in a future long-term prospective study involving repeated measurements in the same patients.
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PMID:Airway inflammation in nonobstructive and obstructive chronic bronchitis with chronic haemophilus influenzae airway infection. Comparison with noninfected patients with chronic obstructive pulmonary disease. 1098 11

Nontypeable Hemophilus influenzae (NTHi) is an important human pathogen in both children and adults. In children, it causes otitis media, the most common childhood infection and the leading cause of conductive hearing loss in the United States. In adults, it causes lower respiratory tract infections in the setting of chronic obstructive pulmonary disease, the fourth leading cause of death in the United States. The molecular mechanisms underlying the pathogenesis of NTHi-induced infections remain undefined, but they may involve activation of NF-kappa B, a transcriptional activator of multiple host defense genes involved in immune and inflammatory responses. Here, we show that NTHi strongly activates NF-kappa B in human epithelial cells via two distinct signaling pathways, NF-kappa B translocation-dependent and -independent pathways. The NF-kappa B translocation-dependent pathway involves activation of NF-kappa B inducing kinase (NIK)--IKK alpha/beta complex leading to I kappa B alpha phosphorylation and degradation, whereas the NF-kappa B translocation-independent pathway involves activation of MKK3/6--p38 mitogen-activated protein (MAP) kinase pathway. Bifurcation of NTHi-induced NIK-IKK alpha/beta-I kappa B alpha and MKK3/6--p38 MAP kinase pathways may occur at transforming growth factor-beta activated kinase 1 (TAK1). Furthermore, we show that toll-like receptor 2 (TLR2) is required for NTHi-induced NF-kappa B activation. In addition, several key inflammatory mediators including IL-1 beta, IL-8, and tumor necrosis factor-alpha are up-regulated by NTHi. Finally, P6, a 16-kDa lipoprotein highly conserved in the outer membrane of all NTHi and H. influenzae type b strains, appears to also activate NF-kappa B via similar signaling pathways. Taken together, our results demonstrate that NTHi activates NF-kappa B via TLR2-TAK1-dependent NIK--IKK alpha/beta-I kappa B alpha and MKK3/6--p38 MAP kinase signaling pathways. These studies may bring new insights into molecular pathogenesis of NTHi-induced infections and open up new therapeutic targets for these diseases.
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PMID:Activation of NF-kappa B by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK-IKK alpha /beta-I kappa B alpha and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells. 1143


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