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)

Pseudomonas aeruginosa is a virulent pathogen and is frequently associated with bacterial keratitis. Recent studies have shown that high levels of interleukin (IL)-1beta and macrophage inflammatory protein-2 are associated with the severity of corneal infection. Interleukin-1beta is a principal inflammatory mediator. Understanding the regulatory role of IL-1beta would provide better understanding of host responses during P. aeruginosa corneal infection. A human corneal epithelial (HCE) cell line and three P. aeruginosa strains were used in this experiment. Confluent HCE cells were challenged with P. aeruginosa and monoclonal antihuman IL-1beta antibody (IL-1beta mAb). The culture supernatants were collected for measuring cytotoxicity and protein levels of IL-1beta, IL-8 and IL-6 by enzyme-linked immunosorbent assay. Results showed that HCE cells expressed low levels of IL-1beta and high levels of IL-6 and IL-8 during P. aeruginosa colonization. Paer1-colonized HCE cells produced higher levels of IL-1beta, IL-6 and IL-8 protein compared to those produced by 6206- and 6294-colonized HCE cells. Administration of IL-1beta mAb decreased the production of IL-8 and IL-6. In conclusion, P. aeruginosa-colonized HCE cells produced low levels of IL-1beta and high levels of IL-6 and IL-8. Neutralizing IL-1beta protein significantly downregulated the production of IL-8 and IL-6.
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PMID:Regulatory role of IL-1beta in the expression of IL-6 and IL-8 in human corneal epithelial cells during Pseudomonas aeruginosa colonization. 1144 62

Erythromycin has been shown to be beneficial for panbronchiolitis, a disorder linked to infection with Pseudomonas aeruginosa. Erythromycin, but not the anti-Pseudomonas antibiotics imipenem, ceftazidime, gentamicin and ciprofloxacin, caused a dose-dependent decrease in the production of tumour necrosis factor (TNF)-alpha by whole blood stimulated with heat-killed P. aeruginosa. The release of interleukin (IL)-10, IL-6, interferon-gamma and IL-8 was inhibited only at the highest erythromycin concentration. Inhibition of TNF-alpha production by erythromycin may, at least in part, explain the efficacy of this macrolide during panbronchiolitis despite its lack of activity for P. aeruginosa.
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PMID:Erythromycin inhibits Pseudomonas aeruginosa-induced tumour necrosis factor-alpha production in human whole blood. 1148

Several recent reports have suggested that airway inflammation may precede infection and relate to an endogenous dysregulation of pro-inflammatory cytokines in cystic fibrosis (CF) airways. Evidence suggests that activation of the nuclear factor kappa B (NFkappaB), which regulates the inflammatory gene transcription, depends on the degradation of the inhibitory factor IkappaBalpha. We show that, in in situ human DeltaF508 CF bronchial tissues, inhibitor factor IkappaBalpha is not present in gland cells, although endogenous levels of chemokine IL-8 are high. These data are confirmed by studying cultured CF human bronchial gland cells, in which a lack of cytosolic IkappaBalpha and high levels of activated NFkappaB, concomitant with IL-8 overproduction (a 13-fold increase) are found when compared to non-CF bronchial gland cells. Interestingly, treatment of CF gland cells with the isoflavone genistein, a well known CFTR mutant Cl(-) channel stimulator, results in a significant decrease ( P < 0.001) in IL-8 production down to levels released by non-CF gland cells. The addition of genistein also reverses the effects of lipopolysaccharide (LPS) Pseudomonas-aeruginosa-induced nuclear translocation of NFkappaB by increasing IkappaBalpha protein level (65%) in CF gland cells. Our data indicate that the induction of IkappaBalpha protein in CF airway glandular epithelial cells may be a novel mechanism by which IL-8-mediated lung inflammatory events are markedly reduced in CF patients, at least at the airway glandular level.
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PMID:Relationship between IkappaBalpha deficiency, NFkappaB activity and interleukin-8 production in CF human airway epithelial cells. 1184 1

Chronic Pseudomonas aeruginosa infections lead to progressive lung tissue destruction in cystic fibrosis (CF) patients. Two bacterial cell-to-cell signals, 3-oxo-C(12)-HSL and C(4)-HSL are required for the production of several extracellular virulence factors. 3-oxo-C(12)-HSL is also required for the development of a differentiated biofilm, induces IL-8 production by epithelial cells and possesses immunomodulatory activities. These two signalling molecules are therefore believed to play a role in the pathogenesis of P. aeruginosa infections, but have never been isolated from infected human tissues. We extracted and quantified the two P. aeruginosa cell-to-cell signals from lung tissues of two CF patients infected by P. aeruginosa. 3-oxo-C(12)-HSL and C(4)-HSL were detected in the lung tissues in fmol/gram, respectively pmol/gram concentrations; the ratio C(4)-HSL/3-oxo-C(12)-HSL exceeded 100 in all tissue samples. Random Amplified Polymorphism DNA genotyping revealed that one genotype was present per lung. In vitro the P. aeruginosa isolates from the two lungs produced 3-oxo-C(12)-HSL, whereas some isolates did not produce detectable C(4)-HSL. Our results suggest that both P. aeruginosa cell-to-cell signals were produced in the lung tissue of these two cystic fibrosis patients.
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PMID:Detection of Pseudomonas aeruginosa cell-to-cell signals in lung tissue of cystic fibrosis patients. 1185 45

Cystic fibrosis (CF) is a complex multisystem disorder caused by mutations in a membrane glycoprotein called the CF transmembrane regulator (CFTR), which has as its major function serving as a Cl- channel. The relationship between defects in CFTR and development of lung disease remains incompletely understood. Chronic lung disease, characterized by persistent infection with a peculiar type of Pseudomonas aeruginosa, bronchiectasis, and airway obstruction is the major cause of morbidity and mortality in CF patients. The inflammatory response to the chronic infection resembles that induced by lipopolysaccharide (LPS) and is mediated primarily by cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6, and IL-8, whose synthesis is activated by the transcription factor nuclear factor kappa B (NF-kappa B). Large numbers of neutrophils dominate the inflammatory response and excessive concentrations of their products create a vicious cycle that becomes injurious rather than protective and eventually claims the life of the patient.
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PMID:Inflammatory mediators in cystic fibrosis lung disease. 1189 30

The cytokines IL-1 beta, IL-6 and the chemokine IL-8 are key mediators of host inflammation. 1 alpha,25-Dihydroxyvitamin D3 (VD3) has been shown to regulate host immune responses in vivo and in vitro. The purpose of this study was to investigate whether the addition of VD3 to human corneal epithelial cells colonized with Pseudomonas aeruginosa altered the expression of IL-1 beta, IL-6 and IL-8. An immortalized human corneal epithelial (HCE) cell line was used in this study. After growth to confluency, HCE cells were challenged with P. aeruginosa strain 6294 in the presence or absence of 10-6 mol/L VD3 for 4 h, 8 h and 12 h. Gene expression of IL-1 beta, IL-6 and IL-8 was detected by reverse transcription-PCR (RT-PCR) from total RNA extracted from HCE cells. Protein concentrations of IL-1 beta, IL-6 and IL-8 in culture supernatants were measured by ELISA. Addition of VD3 to HCE cells colonized with P. aeruginosa significantly inhibited the expression of IL-1 beta and IL-8 mRNA and protein (P < 0.05). Although the expression of IL-6 mRNA was stimulated at 12 h post-challenge (P < 0.05), the expression of IL-6 protein was inhibited at all time points after the addition of VD3. In conclusion, this study demonstrated that VD3 inhibited the P. aeruginosa-induced expression of IL-1 beta, IL-6 and IL-8 in HCE cells, suggesting that this vitamin may have the potential to become a novel anti-inflammatory agent in ocular disease.
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PMID:1 alpha,25-Dihydroxyvitamin D3 inhibits pro-inflammatory cytokine and chemokine expression in human corneal epithelial cells colonized with Pseudomonas aeruginosa. 1212 Dec 22

Ligation of the asialoGM1 Pseudomonas aeruginosa pilin receptor has been demonstrated to induce IL-8 expression in airway epithelial cells via an NF-kappaB-dependent pathway. We examined the signaling pathways required for asialoGM1-mediated NF-kappaB activation in IB3 cells, a human bronchial epithelial cell line derived from a cystic fibrosis (CF) patient, and C-38 cells, the rescued cell line that expresses a functional CF transmembrane regulator. Ligation of the asialoGM1 receptor with specific antibody induced greater IL-8 expression in IB3 cells than C-38 cells, consistent with the greater density of asialoGM1 receptors in CF phenotype cells. AsialoGM1-mediated activation of NF-kappaB, IkappaB kinase (IKK), and ERK was also greater in IB3 cells. With the use of genetic inhibitors, we found that IKK-beta and NF-kappaB-inducing kinase are required for maximal NF-kappaB transactivation and transcription from the IL-8 promoter. Finally, although ERK activation was required for maximal asialoGM1-mediated IL-8 expression, inhibition of ERK signaling had no effect on IKK or NF-kappaB activation, suggesting that ERK regulates IL-8 expression in an NF-kappaB-independent manner.
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PMID:Signaling intermediates required for NF-kappa B activation and IL-8 expression in CF bronchial epithelial cells. 1238 60

The concept that inflammatory gene expression is dysregulated in airway epithelial cells from patients with cystic fibrosis (CF) is controversial. To examine this possibility systematically, responses to inflammatory stimuli were compared in CF airway epithelial cell lines without versus with wild-type CF transmembrane conductance regulator (CFTR) complementation and in tracheobronchial epithelial cells from patients with versus without CF. Epithelial cell expression of the leukocyte adhesion glycoprotein intercellular adhesion molecule-1 (ICAM-1) and release of the neutrophil chemoattractant interleukin (IL)-8 were determined under basal conditions or after exposure to stimuli important in CF airway inflammatory responses. We found that uncorrected CF airway epithelial cell lines inconsistently expressed higher ICAM-1 and IL-8 levels. Human CF tracheobronchial epithelial cells in primary culture released moderately increased IL-8 only after exposure to Pseudomonas aeruginosa. In CF cells with higher IL-8 release, transient expression of wild-type CFTR using an adenoviral vector did not specifically affect cytokine levels. The results indicate that there is considerable variability in airway epithelial cell responses to inflammatory stimuli among different individuals and cell models systems. Although increased ICAM-1 and IL-8 expression are observed in some CF airway epithelial cell models, many CF cells do not exhibit significant dysregulation of these important inflammatory genes.
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PMID:Inflammatory response in airway epithelial cells isolated from patients with cystic fibrosis. 1240 95

As reported previously for Ralstonia solanacearum strain GMI1000, wild-type strains AW1 and K60 were shown to produce Hrp pili. AW1 and K60 mutants lacking Hrp pili still exhibited twitching motility, which requires type 4 pili (Tfp), and electron microscopy revealed that they still made flexuous polar pili. Twitching-positive cells had an extracellular 17 kDa protein that was associated with piliation, and an internal 43-amino-acid sequence of this protein was typical of type 4 pilins. This amino acid sequence is encoded by an open reading frame, designated pilA, in the genomic sequence of GMI1000. PilA is 46% identical to a Pseudomonas aeruginosa type 4 pilin over its entire length and has all the conserved residues and motifs characteristic of type 4 group A pilins. pilA mutants did not make the 17 kDa PilA protein and did not exhibit twitching motility. When compared with its parent, an AW1 pilA mutant was reduced in virulence on tomato plants and in autoaggregation and biofilm formation in broth culture. Unlike AW1, a pilA mutant did not exhibit polar attachment to tobacco suspension culture cells or to tomato roots; it was also not naturally competent for transformation. We reported previously that twitching motility ceases in maturing AW1 colonies and that inactivation of PhcA, a global transcriptional regulator, results in colonies that continue to exhibit twitching motility. Similarly, in broth culture, expression of a pilA::lacZ fusion in AW1 decreased 10-fold at high cell density, but expression remained high in a phcA mutant. In addition, pilA::lacZ expression was positively regulated 10-fold by PehR, a response regulator that is known to be repressed by PhcA. This signal cascade is sufficient to explain why pilA expression, and thus twitching motility, decreases at high cell densities.
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PMID:Ralstonia solanacearum requires type 4 pili to adhere to multiple surfaces and for natural transformation and virulence. 1240 19

The aim of this study was to elucidate the expression of chemokines, their role and regulation in bacterial corneal infection using three bacterial strains (Pseudomonas. aeruginosa- invasive, cytotoxic and contact lens induced acute red eye strains) which have been shown to produce three distinct patterns of corneal disease in the mouse. The predominant chemokine expressed in response to all three strains was MIP-2. Prolonged expression of high levels of MIP-2 was associated with increased severity of corneal inflammation. Significantly reduced disease severity upon administration of anti-MIP-2 antibodies suggested that MIP-2 may play an important role in the pathogenesis of Pseudomonas keratitis at least in part by being a major chemoattractant for polymorphonuclear leukocytes (PMN) recruitment. Interestingly, the numbers of bacteria in eyes with neutralized MIP-2 activity did not decrease even though the severity of the disease was decreased. This implies PMNs as the major destructive factor in microbial keratitis. Further, neutralization of IL-1beta activity alone using monoclonal antibodies resulted in significant reduction of both MIP-2 and KC activity indicating that chemokine levels were regulated by IL-1beta. These studies demonstrate that the regulation of MIP-2 activity may be beneficial in reducing corneal damage during microbial keratitis in rodents and perhaps that regulation of the human homologue of MIP-2, IL-8, may be useful for controlling keratitis in humans.
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PMID:Role and regulation of CXC-chemokines in acute experimental keratitis. 1256 10


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