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)

A longitudinal study was conducted to determine the pathogenesis and effect of immunotherapy (IT) on monocyte function. Production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by peripheral blood monocytes in 31 asthmatic children before and one year after IT was compared. Twenty-two children completed the treatment course, and 13 age-matched healthy children served as controls. Adherent monocytes were isolated and stimulated with either crude mite extract of Dermatophagoid farinae (Df) for 7 days or lipopolysaccharide (LPS) for 3 days. The amount of TNF and IL-1 in culture supernatant was quantified by TNF and IL-1 enzyme-linked immunosorbent assay (ELISA) kits, respectively. The LPS-stimulated TNF production in patients was not different before or after IT (245.8 +/- 110.9 vs. 213.3 +/- 161.6 pg/0.1 ml, p +/- 0.202), but was significantly higher than the control (66.7 +/- 42.7 pg/0.1 ml; p less than 0.0001). The LPS-stimulated IL-1 production was similar among the three groups. When stimulated with Df antigen, monocytes from asthmatic patients produced a greater amount of TNF and IL-1 than did those from the control (p less than 0.001). Furthermore, although the production of TNF decreased after successful IT (360.2 +/- 181.6 vs 243.9 +/- 189.1 pg/0.1 ml, p less than 0.05), the production of IL-1 did not change (679.9 +/- 254.1 vs. 534.8 +/- 257.6 pg/0.1 ml, p greater than 0.05). Thus, repeated long-term administration of allergen (IT) was able to suppress specifically the TNF, but not IL-1 production of monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
J Asthma 1992
PMID:The effect of immunotherapy on interleukin-1 and tumor necrosis factor production of monocytes in asthmatic children. 160 37

Asthma and chronic bronchitis are associated with airway remodelling, and airway macrophages are present in bronchial inflammation. TGF-beta and fibronectin released by alveolar macrophages possess a fibrogenic potency. The potential role of alveolar macrophages in airway remodelling was studied in asthma and chronic bronchitis by the release of TGF-beta and fibronectin. Alveolar macrophages were isolated by bronchoalveolar lavage in 14 control subjects, 14 asthmatics and 14 chronic bronchitics. The spontaneous and lipopolysaccharide (LPS)- or concanavalin A (Con A)-induced release of TGF-beta and fibronectin was measured by ELISA. Alveolar macrophages from chronic bronchitics spontaneously release greater amounts of TGF-beta and fibronectin than those from asthmatic and control subjects. Alveolar macrophages from asthmatics release greater amounts of TGF-beta and fibronectin than those from control subjects. The spontaneous release of TGF-beta is significantly correlated with that of fibronectin. Fibronectin release was significantly reduced after LPS stimulation, and TGF-beta release was significantly increased after LPS stimulation, except in chronic bronchitis patients. Con A increased the release of TGF-beta in cells from normal subjects. This study suggests that activated macrophages play a role in airway remodelling in chronic bronchitis and to a lesser extent in asthma.
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PMID:Release of transforming growth factor-beta (TGF-beta) and fibronectin by alveolar macrophages in airway diseases. 887 Jul 8

We determined the effect of inhaled corticosteroid, budesonide, on the release of the anti-inflammatory cytokine, interleukin-10 (IL-10), and of pro-inflammatory cytokines, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF), from blood monocytes and alveolar macrophages of mild asthmatic subjects in a double-blind, cross-over, placebo-controlled study. Budesonide reduced bronchial hyperresponsiveness and improved baseline FEV1. Alveolar macrophages were obtained by bronchoalveolar lavage performed at the end of each treatment phase. IL-10 from blood monocytes was not altered, but both IL-10 mRNA and protein expression from alveolar macrophages stimulated by lipopolysaccharide and IL-1beta were increased after corticosteroid therapy. By contrast, alveolar macrophages released significantly less MIP-1alpha, IFN-gamma, and GM-CSF after steroid treatment. In comparison to alveolar macrophages from normal nonasthmatic volunteers, those from asthmatic patients released more MIP-1alpha, IFN-gamma, and GM-CSF but lower amounts of IL-10 particularly at baseline and after IL-1beta stimulation. The ability of steroids to inhibit pro-inflammatory cytokines but to enhance the anti-inflammatory cytokine such as IL-10 may contribute to their beneficial actions in asthma. Asthma is characterized by alveolar macrophages exhibiting both an enhanced capacity to release pro-inflammatory cytokines and a reduced capacity to produce IL-10.
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PMID:Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1alpha, granulocyte-macrophage colony-stimulating factor, and interferon-gamma release from alveolar macrophages in asthma. 944 7

The aims of the present study were to determine whether beta2-agonists (short- and long-acting) and a glucocorticoid (budesonide) influence the secretion of a pro-inflammatory cytokine (interleukin-1, [IL-1]) and a granulocyte attractant (leukotriene B4 [LTB4]) and to compare these effects on blood monocyte and alveolar macrophages. Alveolar macrophages (obtained by bronchoalveolar lavage) and blood monocytes from 26 healthy nonsmokers were stimulated with lipopolysaccharide or human serum opsonized zymosan. The influence of four beta2-agonists (salbutamol, terbutaline, formoterol, and salmeterol) and a corticosteroid (budesonide) on the release of interleukin-1beta (IL-1beta) and LTB4 was studied in a dose-response manner (10(-8)-10(-5) mol/L for beta2-agonists and 10(-10)-10(-6) mol/ L for budesonide). The stimulated IL-1beta secretion was significantly greater in blood monocytes than in alveolar macrophages (p < 0.05), but alveolar macrophages were much more capable of secreting LTB4 than were blood monocytes (p < 0.001). Budesonide significantly inhibited the release of IL-1beta from blood monocytes (p < 0.001), but no such effect was observed in alveolar macrophages. Budesonide did not influence the release of LTB4 in either cell type. The beta2-agonists neither influenced the LTB4 nor the IL-beta secretion in either cell type with the exception of formoterol, which stimulated IL-1beta secretion at the highest concentration (10(-5) mol/L, p < 0.05). In conclusion, beta2-agonists exhibited only minor effects on IL-1beta secretion from blood monocytes and no effect on LTB4-secretion from either cell type, and budesonide effectively inhibited the IL-1beta release in blood monocytes, but not in alveolar macrophages. Thus, induced secretion of LTB4 and IL-1beta , and the sensitivity to corticosteroids with regard to IL-1beta secretion, change during the transformation from blood monocytes to alveolar macrophages.
J Asthma 1998
PMID:Effects of beta2-agonists and budesonide on interleukin-1beta and leukotriene B4 secretion: studies of human monocytes and alveolar macrophages. 977 83

Nitric oxide (NO) is an important endogenous regulatory molecule implicated in both proinflammatory and antiinflammatory processes in the lung. Previously, we demonstrated that in human alveolar macrophages (AM), NO decreased inflammatory cytokine production, including that of interleukin-1beta, tumor necrosis factor-alpha and macrophage inflammatory protein-1alpha. One mechanism by which NO could regulate such diverse cytokine production is through effects on the transcription factor nuclear factor-kappaB (NF-kappaB), which controls the expression of the genes for these inflammatory cytokines and growth factors. We therefore investigated whether NO affects NF-kappaB activation in AM in vitro and in vivo. In vitro studies with AM showed that NF-kappaB activation by lipopolysaccharide (LPS) is decreased by NO in a dose-dependent manner. NO prevented an LPS-mediated decrease in the NF-kappaB inhibitory protein IkappaB-alpha. In asthma, airway NO levels are increased, whereas in primary pulmonary hypertension (PPH), airway NO levels are lower than in healthy lungs. In vivo investigations were conducted with freshly isolated AM from healthy controls, asthmatic individuals, and PPH patients. Healthy individuals had airway NO levels of 8 +/- 2 ppb (mean +/- SEM), which is associated with low NF-kappaB activation. Asthma patients with airway NO levels > 17 ppb showed minimal NF-kappaB activation, whereas asthmatic individuals with NO levels </= 17 ppb showed greater NF-kappaB activation. PPH patients with low NO (1 +/- 1 ppb) had prominent NF-kappaB activation. These in vivo studies in asthma and PPH support the in vitro observation of an inverse relationship between NO and NF-kappaB activation. One mechanism by which NO blocks cytokine production involves IkappaB.
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PMID:Nitric oxide blocks nuclear factor-kappaB activation in alveolar macrophages. 1046 Jul 48

Nitric oxide (NO) is increased by gp120 in astrocytes and in monocyte-derived macrophages. Of the gp120 fragments (F1: amino acid 254-274, F2: amino acid 315-329, F3: amino acid 421-438), F1 has been shown to increase NO in astrocytes and gp120 also primes CD4+ T cells for apoptosis. Peripheral blood mononuclear cells (PBMCs) at 10(6)/ml (N = 10) were incubated at 24 and 72 hours in RPMI, 10% CO2 with low doses (100 nM) gp120 and high doses (400 nM) of the smaller fragments. Supernatants were collected and assayed for the relative contribution of gp120 and its fragments on NO production at both time points. Apoptosis was detected by in situ hybridization with and without 1 microgram/ml LPS as superantigen at 72 hours. The major contribution to apoptosis and NO production was from F1. At 24 hours F1 had a 1.9-fold increase from control, whereas F2 and F3 had 1.25- and 1.35-fold increases. At 72 hours both F1 and F2 had a 1.5-fold increase and F3 had a 1.33 increase. Thus, F1 contributed significantly to NO production at 24 hours. Both F1 and F2 had significant contributions to NO production at 72 hours. F1 had the most contribution to apoptosis both with and without lipopolysaccharide (LPS). These findings may contribute to further understanding the mechanism of HIV-induced apoptosis.
Allergy Asthma Proc
PMID:Nitric oxide production and apoptosis by GP120. 1089 16

Asthma severity depends to a great extent on the levels of endotoxin present in the microenvironment. Although favouring a Th1 cytokine response that could be beneficial to the asthmatic, lipopolysaccharide (LPS) aggravates bronchopulmonary inflammation by several mechanisms. These include neutrophil and eosinophil recruitment, and release by activated macrophages of pro-inflammatory cytokines and nitric oxide. LPS exerts its biological actions through its interaction with CD14. The genetic locus of CD14 is close to the genomic region controlling levels of IgE. A polymorphism in the CD14 promoter region seems to favour high serum IgE levels. Genetic influences may thus control circulating levels of sCD14 and by this mechanism modulate Th1/Th2 balance and IgE synthesis. LPS exposure, although hazardous to the asthmatic, seems to exert a role in the maturation of the immune system in children towards a Th1-skewed pattern.
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PMID:Endotoxins, asthma, and allergic immune responses. 1109 Sep 37

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.
Allergy Asthma Proc
PMID:Inflammatory mediators in cystic fibrosis lung disease. 1189 30

Asthma is a complex genetic disorder that is caused by a number of unique gene-gene and gene-environment interactions. The search for asthma susceptibility genes has been complicated by the broad clinical phenotype of asthma, the polygenic inheritance pattern of this disease, and the substantial role of environmental exposures in the development and progression of asthma. Inhaled environmental agents induce several biologic responses in asthmatics; including the induction of acquired and innate immunity that leads to acute and chronic forms of airway inflammation and airway remodeling. Acquired immune responses to protein antigens, such as house dust mite allergen, often induce type 2 T lymphocyte-driven responses (Th2) which appear to be important in atopic asthma. Recent studies by our group and others demonstrate that innate immunity, initiated by inhalation of bacterial and viral pathogens, organic dusts, endotoxin or lipopolysaccharide (LPS), air pollution particulate matter, and ozone, can also cause acute and chronic forms of airflow obstruction, airway inflammation, and even airway remodeling. Emerging evidence indicates that both acquired and innate immune responses in the lung may be influenced by polymorphic genes. For instance, functional polymorphisms in the IL-4 receptor gene are thought to preferentially stimulate acquired Th2 immune responses to inhaled allergens, and we have recently shown that common co-segregating mutations in TLR4 (a transmembrane receptor for LPS) are associated with diminished airway responsiveness to inhaled LPS. These observations suggest that environmental challenges can be used to narrow the phenotype of asthma and allow scientists to investigate unique gene-environment interactions that are involved in the development of biologically specific forms of asthma.
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PMID:TLR4 and LPS hyporesponsiveness in humans. 1204 Sep 19

Stimulation by specific allergens induces inflammatory cytokine production from peripheral blood mononuclear cells (PBMCs) in patients with atopic asthma, but the mechanism remains unknown. PBMCs were collected from six patients with atopic asthma with an immunoglobulin E-radioallergosorbent test score to Dermatophagoides farinae of > or = 4 and six nonatopic healthy subjects (score = 0) using a dish adhesion method after density gradient centrifugation. CD23 expression in PBMCs was analyzed by the fluorescence-activated cell sorting method. PBMCs were incubated with D. farinae or lipopolysaccharide, and production of tumor necrosis factor (TNF) alpha into the supernatant was measured by enzyme-linked immunosorbent assay. After incubation, immunostaining nostaining of the PBMCs with anti-nuclear factor kappa B (NF-kappa B) antibody (anti-p65 antibody against p65 as the subunit of NF-kappa B) was performed, and NF-kappa B activation in extracted nuclear protein was examined by electrophoretic mobility shift assay. CD23 expression was significantly higher in PBMCs from patients with asthma than in the controls (p < 0.01). There was no significant difference in TNF-alpha production by lipopolysaccharide stimulation between the two groups, but D. farinae-specific TNF-alpha production was significantly higher in subjects with asthma than in the controls (p < 0.05). A significant translocation of NF-kappa B to nuclei by D. farinae stimulation was observed in cells from subjects with asthma (p < 0.01). Our results indicated that TNF-alpha production was induced by D. farinae in PBMCs of patients with atopic asthma by the activation of NF-kappa B via CD23. In patients with atopic asthma, CD23-mediated signals may cause proinflammatory cytokine production, which may lead to airway inflammation.
Allergy Asthma Proc
PMID:Production of TNF-alpha by peripheral blood mononuclear cells through activation of nuclear factor kappa B by specific allergen stimulation in patients with atopic asthma. 1263 74


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