Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary infection with mucoid strains of Pseudomonas aeruginosa in present in the majority of cystic fibrosis patients with chronic lung disease. It has been postulated that this mucoid coating may act to decrease lung clearance of Pseudomonas by limiting access of phagocytes, antibodies, and antibiotics to the bacteria. To determine whether mucoid coating of Pseudomonas might decrease intrapulmonary killing, groups of guinea pigs were infected with intrabronchial instillations of equivalent numbers of mucoid and nonmucoid Pseudomonas. For this study, mucoid strains of Pseudomonas were obtained from cystic fibrosis sputa and passaged on blood agar plates to obtain their nonmucoid revertants. Animals were then sacrificed at timed intervals after infection, and quantitative cultures were performed on lung homogenates. In all cases, mucoid challenge strains retained their mucoid morphology after passage in guinea pig lungs. No difference in killing of mucoid and nonmucoid Pseudomonas could be detected at 6, 24, or 48 h after lung infection. Further challenge studies used guinea pigs that were either prevaccinated with lipopolysaccharide P. aeruginosa vaccine or else treated with tobramycin sulfate after infection. Nonvaccinated or untreated controls had reduced intrapulmonary killing of Pseudomonas compared with vaccinees or treated groups (P < 0.02 and P < 0.01, respectively). However, there were no differences in pulmonary killing of mucoid and nonmucoid Pseudomonas in the presence of either specific antibodies or antibiotic. We conclude from these studies that mucoid coating of Pseudomonas does not selectively impede mechanisms of intrapulmonary killing in guinea pig lungs.
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PMID:Influence of mucoid coating on clearance of Pseudomonas aeruginosa from lungs. 678 96

The level of human immunodeficiency virus type 1 (HIV-1) in lymphocytes and mononuclear phagocytes (MP) from the blood and pulmonary alveoli from 14 HIV-1-infected subjects during early (asymptomatic) and late (AIDS) stages of disease and the relationship between virus burden in MP and cytokine expression were assessed. Among asymptomatic subjects, HIV-1 was undetectable or low in both blood monocytes and alveolar macrophages (AM). Among subjects with AIDS, there was a significant increase of HIV-1 in AM but not monocytes. The level of HIV-1 in blood lymphocytes was higher than in either monocytes or AM. AM (but not monocytes) expressed increased levels of lipopolysaccharide-stimulated cytokine mRNA (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6) during both early and late stages of HIV-1 infection regardless of virus load. AM thus may serve as a reservoir for virus in late stages of disease yet contribute to the immunopathogenesis of lung disease in both early and late stages through increased cytokine expression.
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PMID:Relationship between load of virus in alveolar macrophages from human immunodeficiency virus type 1-infected persons, production of cytokines, and clinical status. 827 80

The IgG subclass antibody response to the two parts of Pseudomonas aeruginosa lipopolysaccharide; endotoxic lipid A and the O-polysaccharide, were investigated in a retrospective longitudinal study involving 16 patients with cystic fibrosis and chronic P. aeruginosa lung infection. The purpose of the study was to see if any of the IgG subclasses of either specificity could be used as prognostic markers in the development and subsequent course of the lung disease. IgG2 anti-lipid A, IgG3 anti-lipid A, and IgG2 anti-polysaccharide showed a significant positive correlation with deteriorating pulmonary function already before chronic P. aeruginosa lung infection was diagnosed as well as in subsequent years. The findings suggest antigenic exposure of the patient before chronic infection is detected by routine sputum examinations, and further support our previous findings of a critical role of the IgG subclass response in modulating the course of inflammatory lung damage in these patients.
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PMID:Specific IgG2 antibodies to Pseudomonas aeruginosa lipid A and lipopolysaccharide are early markers of chronic infection in patients with cystic fibrosis. 830 Feb 45

Cystic fibrosis (CF) patients develop progressive cytokine-mediated inflammatory lung disease, with abundant production of thick, tenacious, protease- and oxidant-rich purulent airway secretions that are difficult to clear even with physiotherapy. In the search for a potential treatment, we have tested tyloxapol, an alkylaryl polyether alcohol polymer detergent previously used as a mucolytic agent in adult chronic bronchitis. Tyloxapol inhibits activation of the transcription factor nuclear factor-kappa B (NK-kappa B), reduces resting secretion of the cytokine interleukin-8 (IL-8) in cultured human monocytes, and inhibits lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and the eiconsanoids thromboxane A2 and leukotriene B4 (LTB4). We have previously shown that tyloxapol is a potent antioxidant for hydroxyl radicals ( OH). Tyloxapol (0.05 to 0.1% wt/vol) effectively scavenges the oxidant hypochlorous acid (HOCl; 1 to 7.5 mM) in vitro, and protects from HOCl-mediated lung injury in rats. Tyloxapol also reduces the viscosity of CF sputum (from 463 +/- 133 to 128 +/- 52 centipoise). We conclude that tyloxapol is potentially useful as a new antiinflammatory therapy for CF lung disease, and could possibly promote clearance of secretions in the CF airway.
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PMID:Tyloxapol inhibits NF-kappa B and cytokine release, scavenges HOCI, and reduces viscosity of cystic fibrosis sputum. 881 Jun 19

An unresolved question in cystic fibrosis (CF) research is how mutations of the CF transmembrane conductance regulator, a Cl ion channel, cause airway mucus obstruction leading to fatal lung disease. Recent evidence has linked the CF transmembrane conductance regulator mutation to the onset and persistence of Pseudomonas aeruginosa infection in the airways, and here we provide evidence directly linking P. aeruginosa infection to mucus overproduction. We show that P. aeruginosa lipopolysaccharide profoundly upregulates transcription of the mucin gene MUC 2 in epithelial cells via inducible enhancer elements and that this effect is blocked by the tyrosine kinase inhibitors genistein and tyr-phostin AG 126. These findings improve our understanding of CF pathogenesis and suggest that the attenuation of mucin production by lipopolysaccharide antagonists and tyrosine kinase inhibitors could reduce morbidity and mortality in this disease.
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PMID:Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. 902 66

Overexuberant production of tumour necrosis factor-alpha (TNF-alpha) by macrophages and other cells is thought to contribute to the development of permanent lung damage in many inflammatory conditions. There is a need for an agent, without the side-effects of corticosteroids, which can reduce the production of TNF-alpha by macrophages activated by disease. This study evaluated the effect of thalidomide on lipopolysaccharide (LPS)-induced TNF-alpha production by human alveolar macrophages obtained from patients with tuberculosis and a group of other diseases associated with macrophage activation. Alveolar macrophages obtained by bronchoalveolar lavage from 31 patients (tuberculosis = 12, sarcoidosis = 3, lung cancer = 5, chronic bronchitis = 5, pneumonia = 6) were stimulated with LPS alone or LPS in combination with either thalidomide or dexamethasone. Cell-associated TNF-alpha, as measured by immunochemistry, and TNF-alpha released by macrophages, as assessed by ELISA, were markedly increased when cells were incubated with LPS (P < 0.05), and both were decreased following addition of thalidomide (P < 0.05) or dexamethasone (P < 0.05) to amounts similar to those observed when macrophages were incubated with medium alone. Similarly, TNF-alpha mRNA as measured by in situ hybridization was increased following incubation with LPS (P < 0.05), but this increase was prevented by addition of thalidomide (P < 0.05) or dexamethasone (P < 0.05). The ability of thalidomide to reduce LPS-induced TNF-alpha production by alveolar macrophages was the same when cells from patients with tuberculosis (a disease associated with TNF-alpha production) and cells from patients with the other conditions were compared. The ability of thalidomide to reduce TNF-alpha production by human alveolar macrophages from patients with active lung disease suggests that thalidomide and its analogues may have potential as drugs to reduce TNF-alpha production in disease.
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PMID:Thalidomide reduces tumour necrosis factor-alpha production by human alveolar macrophages. 906 14

The viable motheaten mutant mouse is severely immunodeficient and dies from a naturally occurring progressive pulmonary inflammation at approximately 10 weeks of age. The pulmonary disease is characterized by excessive macrophage accumulation in the lung and fibrosis. We correlated the development of lung injury in viable motheaten mice with tumor necrosis factor-alpha (TNF-alpha) levels in serum and lung. Significantly increased serum TNF-alpha levels were observed by enzyme-linked immunosorbent assay in viable motheaten mice at 4, 6, and 10 weeks of age as compared with normal control littermate mice. These ages correlated well with observed changes in lung wet weights, lung collagen content, and histological evidence of pulmonary inflammation and fibrosis. Qualitative assessment of lung tissue TNF-alpha levels was performed by immunohistochemical staining using immunoperoxidase techniques. These studies revealed increased levels of TNF-alpha in macrophage-like cells in viable motheaten mice from 5 to 10 weeks of age as compared with littermate control animals. Alveolar macrophages isolated from viable motheaten mice produced significantly greater amounts of TNF-alpha when stimulated with lipopolysaccharide compared with alveolar macrophages from control animals. In addition, administration of anti-TNF-alpha antibody to motheaten bone marrow recipient mice decreased the severity of acute lung injury. The results demonstrate a close correlation between the development of pulmonary injury and TNF-alpha levels in this model of spontaneously developing fibrotic lung disease.
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PMID:Role of tumor necrosis factor-alpha in the spontaneous development of pulmonary fibrosis in viable motheaten mutant mice. 935 56

Defensin are 3-4 kDa antimicrobial peptides of which three distinct families have been identified; alpha-defensin, beta-defensins, and insect defensins. Recent investigations have shown that beta-defensins are present in the human airways and may be relevant to the pathogenesis of cystic fibrosis (CF) lung disease. We report here the further characterization of a recently identified mouse beta-defensin gene, Defb1, sometimes referred to as mBD-1, which is homologous to the human airway beta defensin hBD-1. We report that Defb1 is expressed in a variety of tissues including the airways and, similar to hBD-1, is not upregulated by lipopolysaccharide (LPS). Defb1 was found to consist of two small exons separated by a 16-kb intron and cytogenetic, and physical mapping linked it to the alpha defensin gene cluster on mouse Chromosome (Chr) 8. Functional studies demonstrate that, like hBD-1, Defb1 demonstrates a salt-sensitive antimicrobial activity against Pseudomonas aeruginosa. Of relevance to CF lung disease is the fact that neither the hBD-1 nor the mBD-1 peptides are active against Burkholderia cepacia.
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PMID:Mouse beta defensin-1 is a functional homolog of human beta defensin-1. 958 33

Bacterial infection of the lung is associated with mucin overproduction. In partial explanation of this phenomenon, we recently reported that supernatant from the Gram-negative organism Pseudomonas (P.) aeruginosa contained an activity that upregulated transcription of the MUC 2 mucin gene [J.-D. Li, A. Dohrman, M. Gallup, S. Miyata, J. Gum, Y. Kim, J. Nadel, A. Prince, C. Basbaum, Transcriptional activation of mucin by P. aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease, Proc. Natl. Acad. Sci. U.S.A., 94 (1997) 967-972]. The purpose of the present study was to determine whether mucin genes other than MUC 2 are so regulated and whether Gram-positive organisms also contain mucin stimulatory activity. Results from in situ hybridization and RNase protection assays showed that P. aeruginosa upregulates MUC 5AC as well as MUC 2 in both bronchial explants and cultured airway epithelial cells. The upregulation of both genes by P. aeruginosa can be mimicked by lipopolysaccharide (LPS) and can be blocked by the tyrosine kinase inhibitor genistein. In addition, both genes are upregulated by a variety of Gram-positive as well as Gram-negative organisms showing the same rank order of potency. These data indicate the existence of a general mechanism by which epithelial cells respond to the presence of bacteria by increasing mucin synthesis.
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PMID:Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria. 963 Jun 59

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that appears to play a significant role in the development of neonatal chronic lung disease (CLD). Inflammation and CLD are also associated with respiratory tract colonization with genital mycoplasmas. The possible protective roles of surfactant in mitigating the inflammatory response to these microbes were investigated. Murine RAW 264.7 macrophages were preincubated with an exogenous surfactant and exposed overnight to sterile media, lipopolysaccharide (LPS), Mycoplasma hominis, or Ureaplasma urealyticum. Macrophages released TNF-alpha in response to challenge with LPS, U. urealyticum, and M. hominis in a concentration-dependent fashion. Surfactant suppressed LPS and M. hominis induced TNF-alpha production in a dose-dependent manner but suppressed U. urealyticum-mediated TNF-alpha production only at the higher dose tested. Similar effects were seen in hyperoxia (95% O2). Thus, exogenous bovine surfactant significantly inhibits the production of TNF-alpha by murine macrophages stimulated with genital mycoplasmas and bacterial LPS.
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PMID:Exogenous bovine surfactant suppresses tumor necrosis factor-alpha release by murine macrophages stimulated by genital mycoplasmas. 980 43


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