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)

Urinary tract epithelial cells (T 24/83) are able to express interleukin (IL)-6, IL-8, platelet-derived growth factor (PDGF) and tumour necrosis factor-alpha, but not IL-1 beta, IL-2, IL-4 and IL-10 in response to an infection with uropathogenic bacteria. The process of cytokine secretion is time dependent, with a significant increase in the cytokine activity after 60 min. The expression of virulence factors of the bacteria does not seem to play a role. The interaction between bacterial products (e.g. lipopolysaccharide) and/or bacterial adhesion mediated by adhesins and specific receptor molecules of cell surfaces may be responsible for the activity of mediator protein expression in the epithelial cells. The release of PDGF and IL-8 was found to be higher when due to Escherichia coli HB 101 (rough form) than that caused by other bacterial strains. Citrobacter CB 3009 provoked the highest level of IL-6. The PDGF level correlated significantly with IL-6 and IL-8 values (P<0.001). There was a significant correlation between the time-dependent release of IL-6 and IL-8 (P<0.05). In epithelial cytokine response to bacterial infection, the reaction of the epithelial cells may modify themselves (e.g. internalization of bacteria) and the immuno-regulatory processes that are caused by infection and responsible for parenchymal injury.
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PMID:Secretion of cytokines by uroepithelial cells stimulated by Escherichia coli and Citrobacter spp. 1129 4

It is unclear whether inflammation in the cystic fibrosis (CF) lung relates predominantly to bacterial infection, or occurs as a direct consequence of mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. Interleukin (IL)-8 secretion from CF and non-CF cell lines, and from CF and non-CF human primary nasal epithelial cells incubated with or without Pseudomonas aeruginosa, was measured. Activation of nuclear factor-kappaB (NF-kappaB) in unstimulated CF and non-CF nasal epithelial cells, cell lines and murine tissues was measured by gel-shift assays. No significant difference in basal IL-8 production or NF-kappaB activation was observed between CF and non-CF primary nasal cells. However, CF cells exhibited a significantly (p<0.01) increased IL-8 secretion following P. aeruginosa stimulation. Equalization of the increased P. aeruginosa adherence observed in CF cells, to non-CF levels, resulted in comparable IL-8 secretion. Further, IL-8 production did not differ with mutations which result in either correctly localized CFTR, or in partial/total mislocalization of this protein. Similar levels of NF-kappaB activation were observed in a number of organs of wildtype and CF mice. Finally, IL-8 secretion and NF-kappaB activity were not consistently increased in CF cell lines. Cos-7 cell transfection with plasmids expressing deltaF508 or G551D mutant CFTR protein resulted in increased activation of a p50-containing NF-kappaB complex, but IL-8 secretion was similar to wild-type cells. The authors conclude that the stimulus produced by Pseudomonas aeruginosa is the predominant inflammatory trigger in their models.
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PMID:Inflammation in cystic fibrosis airways: relationship to increased bacterial adherence. 1130 53

In a phase IV, open-label study, 25 patients with clinically stable chronic sinusitis and persistent maxillary sinus inflammation were treated for 14 days with clarithromycin 500 mg twice daily. Biopsy specimens of the maxillary sinus mucosa were obtained pretreatment and evaluated for macrophages (CD68), eosinophils (MBP), elastase, interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha), and activity of eosinophils (EG2), as well as edema score. Clinical signs and symptoms were assessed pretreatment, at the end of treatment, and 1 and 2 weeks later. Statistically significant reductions (P < or = .05) from pretreatment were observed for all markers of sinus mucosal inflammation, including CD68, EG2, elastase, IL-6, IL-8, TNF-alpha, and edema score, with a trend to decreased total eosinophil count. Improvement was observed for all clinical signs and symptoms of chronic sinusitis--sinus pain, sinus headache, nasal congestion, nasal discharge, and mucopurulent discharge--up to 14 days after the end of treatment. Cultures to evaluate persistent infection with Chlamydia pneumoniae showed negative results. Significant reductions in various markers of sinus mucosal inflammation support the role of clarithromycin in modulating immunologic responses. Improvement of clinical signs and symptoms in patients with chronic inflammatory sinusitis not meeting criteria for known or presumed bacterial infection was also noted up to 2 weeks after completion of a 14-day course of clarithromycin.
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PMID:Anti-inflammatory activity of clarithromycin in adults with chronically inflamed sinus mucosa. 1144 71

Infection with Neisseria meningitidis serogroup B is responsible for fatal septicemia and meningococcal meningitis. The severity of disease directly correlates with the production of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, and IL-8. However, the source of these cytokines has not been clearly defined yet. Since bacterial infection involves the activation of dendritic cells (DCs), we analyzed the interaction of N. meningitidis with monocyte-derived DCs. Using N. meningitidis serogroup B wild-type and unencapsulated bacteria, we found that capsule expression significantly impaired neisserial adherence to DCs. In addition, phagocytic killing of the bacteria in the phagosome is reduced by at least 10- to 100-fold. However, all strains induced strong secretion of proinflammatory cytokines TNF-alpha, IL-6, and IL-8 by DCs (at least 1,000-fold at 20 h postinfection [p.i.]), with significantly increased cytokine levels being measurable by as early as 6 h p.i. Levels of IL-1beta, in contrast, were increased only 200- to 400-fold at 20 h p.i. with barely measurable induction at 6 h p.i. Moreover, comparable amounts of cytokines were induced by bacterium-free supernatants of Neisseria cultures containing neisserial lipooligosaccharide as the main factor. Our data suggest that activated DCs may be a significant source of high levels of proinflammatory cytokines in neisserial infection and thereby may contribute to the pathology of meningococcal disease.
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PMID:Interaction of Neisseria meningitidis with human dendritic cells. 1159 66

Bacterial infection of the pulp and root canal system leads to the recruitment of immunocompetent cells in the periapex and stimulates inflammatory cell responses to produce a variety of inflammatory mediators. Cytokines, reactive oxygen intermediates, and reactive nitrogen intermediates are frequently found at sites of acute inflammation. In this study, we measured the levels of interleukin (IL)-8 and nitric oxide (NO) in the periapical exudate (PE) from human periapical lesions and investigated the association of these mediators with the clinical symptoms of periapical periodontitis. PE samples were collected from root canals during routine endodontic treatments. The IL-8 concentration was measured by the enzyme-linked immunosorbent assay, and the NO level was measured as nitrite/nitrate concentration assayed by the Griess reaction. Detectable levels of IL-8 and nitrite/nitrate were found in 24 and 19 of 27 PE-samples, respectively. Although PE-IL-8 and nitrite/nitrate concentration showed a broad range, a significantly positive correlation was found between both mediators. Also, significantly higher IL-8 levels were found in PE from lesions that had painful symptoms at the sampling visit. However, there was no relationship between elevated NO levels and clinical symptoms. These results suggest that the up-regulation of IL-8 may have a critical role in the development of the symptoms of periapical disease.
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PMID:Production of interleukin-8 and nitric oxide in human periapical lesions. 1177 82

In the present study, we investigated the mRNA expression of inflammatory cytokines, including interleukin (IL)-1 alpha, IL-6, IL-8, and granulocyte macrophage colony-stimulating factor (GM-CSF), and beta defensin 1 (BD-1), an antimicrobial peptide, in the epithelial rests of Malassez in vitro. A reverse transcription-polymerase chain reaction (RT-PCR) assay was performed in order to observe the expression of these mRNAs. The effect of lipopolysaccharide (LPS) on the mRNA expression was also studied by quantitative RT-PCR assay, with a LightCycler, using the double-stranded DNA dye SYBR Green I. The mRNAs of the four kinds of inflammatory cytokines and BD-1 were detected in the epithelial cells under normal culture conditions. Immunocytochemical staining showed the expression of CD14, a receptor for LPS, on the epithelial cells. The mRNA expressions of IL-1 alpha, IL-6, IL-8, and GM-CSF were upregulated by stimulation with LPS, in a dose- and time-dependent manner. Epithelial cells incubated with 1000 ng/ml of LPS for 6 h showed the most significant upregulation of the cytokine mRNAs. On the other hand, no obvious alteration of BD-1 expression by LPS stimulation was observed. The results indicated that the epithelial rests of Malassez may actively participate in the inflammatory response to bacterial infection, and that they play an important role in the defense mechanism of the radicular cyst.
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PMID:Expression of inflammatory cytokines and beta-defensin 1 mRNAs in porcine epithelial rests of Malassez in vitro. 1179 93

Lipopolysaccharide (LPS) is a key inflammatory mediator. It has been proposed to function as an important molecule that alerts the host of potential bacterial infection. Although highly conserved, LPS contains important structural differences among different bacterial species that can significantly alter host responses. For example, LPS obtained from Porphyromonas gingivalis, an etiologic agent for periodontitis, evokes a highly unusual host cell response. Human monocytes respond to this LPS by the secretion of a variety of different inflammatory mediators, while endothelial cells do not. In addition, P. gingivalis LPS inhibits endothelial cell expression of E-selectin and interleukin 8 (IL-8) induced by other bacteria. In this report the ability of P. gingivalis LPS to activate p38 mitogen-activated protein (MAP) kinase was investigated. It was found that p38 MAP kinase activation occurred in response to P. gingivalis LPS in human monocytes. In contrast, no p38 MAP kinase activation was observed in response to P. gingivalis LPS in human endothelial cells or CHO cells transfected with human Toll-like receptor 4 (TLR-4). In addition, P. gingivalis LPS was an effective inhibitor of Escherichia coli-induced p38 MAP kinase phosphorylation in both endothelial cells and CHO cells transfected with human TLR-4. These data demonstrate that P. gingivalis LPS activates the LPS-associated p38 MAP kinase in monocytes and that it can be an antagonist for E. coli LPS activation of p38 MAP kinase in endothelial and CHO cells. These data also suggest that although LPS is generally considered a bacterial component that alerts the host to infection, LPS from P. gingivalis may selectively modify the host response as a means to facilitate colonization.
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PMID:Porphyromonas gingivalis lipopolysaccharide is both agonist and antagonist for p38 mitogen-activated protein kinase activation. 1189 49

Cystic fibrosis (CF) lung disease is characterized by a self-perpetuating cycle of airway obstruction, chronic bacterial infection, and vigorous inflammation that results in structural damage to the airway. CF patients have a predilection for infection with a limited spectrum of distinctive bacteria that initiate a vigorous inflammatory response which is more harmful than protective. The airway epithelial cell, which normally expresses the cystic fibrosis transmembrane conductance regulator (CFTR), directs the inflammatory response. Defects in CFTR are associated with increased production of pro-inflammatory mediators including IL-8, a potent neutrophil chemoattractant that stimulates the influx of massive numbers of neutrophils into the airways. These neutrophils are the primary effector cells responsible for the pathological manifestations of CF lung disease. Documented deficiencies in immunoregulatory molecules such as IL-10 likely contribute to the generation of the excessive and persistent inflammatory response. Since inflammation is a key contributor to the pathogenesis of CF lung disease, anti-inflammatory therapy must assume a larger role in CF until a cure is discovered. To date, attention has focused primarily on the therapeutic potential of systemic and inhaled corticosteroids and the non-steroidal anti-inflammatory drug (NSAID) ibuprofen. Development of new anti-inflammatory therapies that impact intracellular signaling pathways and cell-cell communication molecules likely will have the greatest impact on limiting the excessive production of the inflammatory mediators in the CF lung, thereby slowing the decline in lung function and improving survival.
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PMID:The role of inflammation in the pathophysiology of CF lung disease. 1216 6

Dengue virus (DV) primarily infects blood monocytes (MO) and tissue macrophages (M phi). We have shown in the present study that DV can productively infect primary human MO/M phi regardless of the stage of cell differentiation. After DV infection, the in vitro-differentiated MO/M phi secreted multiple innate cytokines and chemokines, including tumor necrosis factor alpha, alpha interferon (IFN-alpha), interleukin-1 beta (IL-1 beta), IL-8, IL-12, MIP-1 alpha, and RANTES but not IL-6, IL-15, or nitric oxide. Secretion of these mediators was highlighted by distinct magnitude, onset, kinetics, duration, and induction potential. A chemokine-to-cytokine hierarchy was noted in the magnitude and induction potential of secretion, and a chemokine-to-cytokine-to-chemokine/Th1 cytokine cascade could be seen in the production kinetics. Furthermore, we found that terminally differentiated MO/M phi cultured for more than 45 days could support productive DV infection and produce innate cytokines and chemokines, indicating that these mature cells were functionally competent in the context of a viral infection. In addition, DV replication in primary differentiated human MO/M phi was enhanced and prolonged in the presence of lipopolysaccharide (LPS), and LPS-mediated synergistic production of IFN-alpha could be seen in DV-infected MO/M phi. The secretion of innate cytokines and chemokines by differentiated MO/M phi suggests that regional accumulation of these mediators may occur in various tissues to which DV has disseminated and may thus result in local inflammation. The LPS-mediated enhancement of virus replication and synergistic IFN-alpha production suggests that concurrent bacterial infection may modulate cytokine-mediated disease progression during DV infection.
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PMID:Activation of terminally differentiated human monocytes/macrophages by dengue virus: productive infection, hierarchical production of innate cytokines and chemokines, and the synergistic effect of lipopolysaccharide. 1220 65

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite improvements in treatment, pulmonary disease still remains the primary cause of death among these patients. In order to introduce a normal CFTR gene copy into airway epithelial cells, adenoviral vectors (AV) have been developed. AV are known to induce an inflammatory reaction that limits transgene expression, and can be potentially harmful. No human study has clearly monitored simultaneously, systemic and local inflammatory reaction, during AV administration. We report here the levels of C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 receptor antagonist (IL-1Ra) in plasma and bronchoalveolar lavage fluid (BALF) from six cystic fibrosis patients receiving AV encoding CFTR (AdCFTR). AdCFTR was administered to three cohorts of two patients into the nose on day 0, at doses ranging from 105 to 4 x 108 plaque-forming units (pfu), followed, on day 1, by aerosolization of 107 to 5.4 x 108 pfu. In order to ensure that patients were in the best clinical condition, and to further attenuate the broncho-pulmonary inflammation secondary to bacterial infection, they received antibiotic therapy, two weeks prior to AdCFTR administration, until 9 to 11 days after. We found that antibiotics markedly decreased CRP, TNF-alpha, IL-6, IL-1Ra levels in blood. In BALF, antibiotics slightly decreased TNF-alpha levels but had no effect on IL-8 and IL-1Ra, while IL-6 levels increased. AdCFTR administration did not induce any systemic or local cytokine release. In both blood and BALF, CRP, IL-8, IL-1Ra, TNF-alpha decreased, while IL-6 levels increased between day -7 and day 3. One patient presented an asymptomatic increase of all parameters in the BALF on day 7. Twenty one days later, he displayed a clinical deterioration suggestive of an exacerbation. In conclusion, this study demonstrates that antibiotic administration tends to attenuate systemic but not local broncho-pulmonary inflammation in CF patients. In the setting of our study, AdCFTR administration did not induce cytokine release. Further studies are necessary to investigate other inflammatory markers and the mechanisms involved during AV-mediated gene transfer for a better understanding of the immune reaction, which continues to hamper the development of gene therapy for CF patients.
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PMID:Cytokine pattern in cystic fibrosis patients during antibiotic therapy and gene therapy using adenoviral vector. 1223 76


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