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

We determined if alveolar macrophages (AMs) from infants with severe recurrent wheezing episodes release increased amounts of tumour necrosis factor-alpha (TNF-alpha), as described in adults with asthma. We compared TNF-alpha release by unstimulated and lipopolysaccharide-stimulated AMs obtained by bronchoalveolar lavage in 13 wheezy and seven nonwheezy infants (aged 6-36 months) and analysed its regulation by dexamethasone. Metabolites in cell supernatants were quantified by enzyme-linked immunosorbent assay (ELISA) (TNF-alpha) or radioimmunoassay (thromboxane B2 and prostaglandin E2). Comparison of results was performed by the Mann-Whitney U-test and values were expressed as median (interquartile range) in ng x 10(6) cells(-1). Resting AMs from wheezy infants released larger amounts of TNF-alpha and thromboxane B2 as compared to controls: 2.67 (0.89-8.33) vs 0.48 (0.25-1.08) and 75.63 (38.07-158.91) vs 10.03 (7.36-76.08), respectively (p<0.05). When stimulated overnight with bacterial lipopolysaccharide, AMs from both groups released similar amounts of metabolites. Dexamethasone induced a consistent inhibition of the lipopolysaccharide-stimulated release of all the mediators. Our results show that alveolar macrophages from wheezy infants are activated to release increased amounts of tumour necrosis factor-alpha, as in asthma, and suggest that infants with recurrent wheezing may eventually benefit from treatment with glucocorticoids.
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PMID:Increased spontaneous release of tumour necrosis factor-alpha by alveolar macrophages from wheezy infants. 927 17

Respiratory syncytial virus (RSV) bronchiolitis is associated with subsequent recurrent wheezing episodes. To determine whether cytokine responses during infection can be of predictive value for the development of recurrent wheezing, we performed a follow-up study in 50 hospitalized children with RSV bronchiolitis. Monocyte and lymphocyte cytokine responses in vitro were studied during the acute phase of disease, and again during the convalescent phase, 3 to 4 wk later. Monocyte cytokine responses, including interleukin-10 (IL-10), were measured in whole blood cultures, stimulated with lipopolysaccharide and interferon-gamma (LPS + IFN-gamma). In addition, T-cell cytokine responses, including IFN-gamma and IL-4 production, were measured in whole-blood cultures stimulated with phytohemagglutinin (PHA) or alphaCD2 + alphaCD28. Cytokine responses were analyzed in relation to the development of recurrent episodes of wheezing, documented by parents in a diary during a 1-yr follow-up period. IL-10 responses during the acute phase of RSV bronchiolitis were comparable to those in healthy control subjects. During the convalescent phase, IL-10 responses were significantly increased in patients as compared with those in healthy control subjects (p < 0.001). At follow-up, 27 children (58%) had recurrent episodes of wheezing. IL-10 levels, measured during the convalescent phase, were significantly higher in patients who developed recurrent wheezing during the year after RSV bronchiolitis than in patients without recurrent episodes of wheezing (p = 0.006). Moreover, IL-10 responses during the convalescent phase correlated significantly with the number of wheezing episodes (r = 0.42, n = 46, p = 0.004). Interestingly, no association was found between IFN-gamma responses, IL-4 responses, or IFNgamma/IL-4 ratios and recurrent wheezing. We conclude that monocyte IL-10 responses in vitro upon stimulation with nonspecific stimuli may have predictive value for the development of recurrent wheezing after RSV bronchiolitis. Moreover, our results indicate that not only allergen-driven Th2 cytokine responses can lead to asthmatic symptoms but also virus-induced changes in cytokine responses may result in asthmatic symptoms.
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PMID:Monocyte IL-10 production during respiratory syncytial virus bronchiolitis is associated with recurrent wheezing in a one-year follow-up study. 1080 48

Microbial exposure has been indicated as significant in the development of asthma and allergy among children. The aim of the study was to test whether microbial exposure and allergens in the school environment are associated with asthmatic symptoms in pupils. Data on asthmatic symptoms and respiratory infections were collected through a questionnaire survey among 1993 pupils aged 11-15 yr in 10 randomly selected schools in Taiyuan, China. Settled dust in classrooms was analysed using tandem gas chromatography-mass spectrometry for 3-hydroxy fatty acids, marker of lipopolysaccharide (LPS) from endotoxin, muramic acid (MuA), marker of bacteria and ergosterol (Erg) for fungi, quantifying both culturable and non-culturable microbes. A total of 29.8% reported daytime attacks of breathlessness, 8.4% wheeze and 1.2% had doctor's diagnosed asthma. Generally, MuA was negatively associated with wheeze and daytime attacks of breathlessness, the latter of which was negatively associated with Erg to a weaker extent. Total concentration of LPS was positively associated with daytime attacks of breathlessness, but shorter lengths of LPS, C10, C12 and C14 LPS were negatively associated with either wheezing or daytime attacks of breathlessness. For MuA and C10 and C12 of LPS, the associations were independent of airborne allergens and classroom crowdedness, and even independent of the other two microbial markers for MuA. Microbial exposure indicated by certain chemical markers (e.g. MuA) could be protective for asthmatic symptoms, but for LPS (endotoxin), the picture is more complex, varying by different lengths of fatty acids of LPS.
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PMID:Asthmatic symptoms among pupils in relation to microbial dust exposure in schools in Taiyuan, China. 1822 61

Asthma is a leading chronic childhood illness in the US. To gain further insight into the pathophysiology of childhood asthma, we studied markers of airway inflammation and possible triggers such as bacterial lipopolysaccharide (LPS) in 18 children with chronic asthma and persistent wheezing who underwent clinically indicated bronchoscopy and bronchoalveolar lavage (BAL). We predominantly found neutrophilic airway inflammation associated with increased levels of IL-8, metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP-1) and MMP-9/TIMP-1 ratio. A significant correlation was found between levels of LPS in BAL and airway neutrophils in BAL from a subgroup of children who had a tendency of increased levels of MMP-9 and TIMP-1, suggesting that increased LPS levels in BAL may contribute to chronic airway inflammation and early remodeling. Our data highlight the importance of defining chronic triggers of early airway inflammation in children and characterizing their inflammation, considering the use of bronchoscopy and BAL. Increased knowledge of airway inflammation in children may help prevent a more severe asthma phenotype and lead to environmental control measures and new treatment strategies to intervene against the establishment of irreversible inflammation.
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PMID:Neutrophilic airway inflammation and association with bacterial lipopolysaccharide in children with asthma and wheezing. 1866 88

Endotoxin or lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria. Like aeroallergens, LPS is ubiquitous in our living environment. Epidemiology studies in young children have found that LPS exposure at home is inversely correlated with the development of atopic diseases, thus the 'hygiene hypothesis' for allergic diseases. However, positive association has also been found between indoor LPS exposure and the development of wheezing or asthma in children. In humans, experimental exposure to LPS in the airways can cause inflammatory responses and lung function changes directly or modulate responses to allergens indirectly, particularly in those with asthma. In animal studies, experimental exposure to LPS has generated some conflicting, sometimes opposite, results in host responses to allergen stimulation. In this article, we will review recent advances in our understanding of the immunomodulating effects of LPS on allergen-induced responses and analyse some of the possible reasons for the inconsistent findings.
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PMID:Immunomodulating effects of endotoxin in mouse models of allergic asthma. 2044 74

Allergic asthma is a chronic lung disease characterized by wheezing, coughing, chest tightness and shortness of breath. Clinically, the treatments against asthma focus on controlling the symptoms rather than inhibiting recurrence radically. Additionally, local and systemic side effects caused by current treatments are worthy of attention. Therefore, a novel therapeutic strategy against asthma is needed. Asatone is a pharmacologically active component from Radix et Rhizoma Asari, which has anti-inflammatory effects in lipopolysaccharide-induced lung injury. In the present study, we showed that asatone could protect mice against OVA-induced asthma, as manifested by attenuating inflammation infiltration, mucus production, and airway hyperreactivity and suppressing the elevation of IL-4, IL-5, and IL-13 in broncho-alveolar lavage fluid. Overall, results of the present study support use of asatone as a potent therapeutic strategy for clinical treatment of allergic asthma.
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PMID:Protective activity of asatone against ovalbumin-induced allergic asthma. 3316 54