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)

Interleukin-10 or cytokine synthesis inhibitory factor has important antiinflammatory activities in immune diseases. We speculated that diminished IL-10 production in asthma would permit the unopposed synthesis of proinflammatory cytokines, contributing to the development and severity of asthma. Our data demonstrate constitutive secretion of IL-10 into bronchoalveolar lavage (BAL) fluid of normal, nonasthmatic subjects (130 +/- 61 pg/ml; n = 8). Asthmatic patients' BAL fluid was characterized by diminished concentrations of IL-10 (9 +/- 18 pg/ml; n = 8; p < 0.01 compared with that of normal subjects). By using the RNA-based polymerase chain reaction, we demonstrated that diminished IL-10 occurred as a result of inhibition of transcription. IL-10 transcription, but not protein, was observed at the time of the late asthmatic response. We speculate that the subsequent appearance of IL-10 protein could contribute to the resolution of the late asthmatic response. Similar to what was observed in the BAL fluid, peripheral blood mononuclear cells of patients with asthma demonstrated decreased spontaneous (0.01 +/- 0.01 ng/ml-asthmatic and 0.09 +/- 0.04 ng/ml-normal; p < 0.05) and stimulated (0.60 +/- 0.22 ng/ml-asthmatic and 1.69 +/- 0.49 ng/ml-normal; p < 0.05) IL-10 production compared with normal subjects. In support of the hypothesis that IL-10 mitigates the development of inflammation, we demonstrated that the addition of a neutralizing anti-IL-10 antibody to resting peripheral blood mononuclear cell cultures of normal subjects stimulated the spontaneous production of interferon-gamma (10.4 +/- 4.3 to 152.4 +/- 23.6 ng/ml; p < 0.01). Finally, we reasoned that corticosteroids might exert at least part of their antiinflammatory activity through the induction of IL-10 secretion. However, methylprednisolone inhibited the lipopolysaccharide-stimulated production of IL-10 (2.34 +/- 0.49 ng/ml IL-10 with lipopolysaccharide alone to 1.11 +/- 0.38 ng/ml in the additional presence of 10(-6) mol/L methylprednisolone; p < 0.05).
 ...
PMID:Interleukin-10 regulation in normal subjects and patients with asthma. 864 25

The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
 ...
PMID:Intercellular adhesion molecule-1. 883 67

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.
 ...
PMID:Release of transforming growth factor-beta (TGF-beta) and fibronectin by alveolar macrophages in airway diseases. 887 Jul 8

In allergic asthma, inhalation of antigen provokes an early increase in microvascular permeability with protein extravasation and a delayed recruitment of inflammatory cells. We showed that similar concentrations of lipopolysaccharide (LPS) are present in bronchoalveolar lavage fluid (BALF) in 12 subjects without asthma (86.5 +/- 53.8 pg/ml) and 12 subjects with mild asthma (111 +/- 37.0 pg/ml). These LPS levels are insufficient to stimulate cytokine release without accessory molecules. BALF obtained 24 h after segmental ragweed antigen challenge in 11 asthmatics allergic to ragweed contained increased levels of two LPS accessory molecules compared with preantigen BALF, 158-fold more LPS-binding protein (LBP) 4.83 +/- 2.02 vs. 742 +/- 387 ng/ml; P < 0.03) and 31.6-fold more soluble CD14 (sCD14) (3.45 +/- 1.04 vs. 110 +/- 51.6 ng/ml; P < 0.02). Postantigen BALF enhanced binding of fluorescein-conjugated LPS to CD14-bearing THP-1 cells and supported LPS-induced non-CD14-bearing endothelial cell expression of intercellular adhesion molecule-1 and interleukin-6, indicating functional LBP and sCD14. We suggest that extravasation of LBP and sCD14 into the bronchoalveolar compartment after antigen inhalation may enhance the capacity of inhaled or aspirated LPS to activate an inflammatory cascade that may amplify the inflammatory response to inhaled antigen in some asthmatics.
 ...
PMID:Asthma and endotoxin: lipopolysaccharide-binding protein and soluble CD14 in bronchoalveolar compartment. 896 7

In this study we evaluated antigen-specific in vitro responses of peripheral blood lymphocytes to lipopolysaccharide (LPS)-depleted food allergens in children who reacted to food challenge (cow's milk or hen's egg) with a deterioration of their atopic dermatitis (AD). Some of the children showed immediate symptoms (urticaria, bronchial asthma or gastrointestinal symptoms) as well. The proliferation of casein-stimulated lymphocytes from children reacting to cow's milk (age 0.7-5.9 years) was significantly higher (P < 0.01) than the proliferation of lymphocytes from 15 children with AD without milk allergy (age: 2.1-9.1 years). Twenty-eight T-cell clones (TCC) were established from the blood of three children sensitized to cow's milk and hen's egg who reacted to double-blind, placebo-controlled oral food challenge both with a deterioration of AD and with immediate symptoms. Surprisingly, 16 of 28 casein- or ovalbumin-specific TCC were CD8+. All TCC produced high amounts of IFN-gamma upon stimulation with concanavalin A. In addition, 75% of the CD4+ TCC and 44% of the CD8+ TCC secreted IL-4. Our results indicate that: (i) food-specific proliferation of blood lymphocytes can be detected in patients with clinically relevant food allergy with LPS-depleted allergens in vitro and (ii) circulating food-specific lymphocytes are CD4+ and CD8+ T cells with the capacity of producing both type 1 and type 2 cytokines.
 ...
PMID:The role of circulating food antigen-specific lymphocytes in food allergic children with atopic dermatitis. 897 15

In the rat, plasma leakage in various vascular beds, including the whole lung, occurs after administration of lipopolysaccharide (LPS). LPS-induced microvascular plasma leakage in many organs is associated with an enhanced formation of nitric oxide (NO) after the induction of nitric oxide synthase (iNOS). However, there is limited information concerning the relationship between NO and plasma leakage into the airways. LPS (10 mg/kg, intravenously) caused a significant leakage of Evans blue dye, a marker of microvascular permeability, at 240 min in the trachea which was inhibited by the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, intravenously), or dexamethasone (1 mg/kg, intravenously). This effect was paralleled by an increase in calcium-independent iNOS activity, assessed by measuring the conversion of radiolabeled L-arginine to L-citrulline, in LPS-treated animals. In contrast, L-NAME significantly increased plasma leakage in the trachea of vehicle-treated rats and this effect was inhibited by indomethacin. These results suggest that under "physiological" conditions endogenous NO suppresses plasma leakage but when iNOS is expressed the increased production of NO enhances plasma leakage. These findings may implicate a role for NO in the maintenance of airway function and in the inflammatory process occurring in diseases such as asthma, where iNOS is known to be expressed.
 ...
PMID:Dual action of nitric oxide on airway plasma leakage. 911 19

Cells respond to a range of cytokines and other inflammatory stimuli by selectively expressing a wide range of genes. These proinflammatory signals bind to receptors and initiate intracellular signalling cascades. This results in the activation of proinflammatory deoxyribonucleic acid (DNA)-binding proteins or transcription factors such as activator protein-1 (AP-1) or nuclear factor-kappa B (NF-kappa B). Following activation, these factors bind to specific recognition sequences in the control regions (promoters) of target genes causing modulation of gene transcription. Furthermore, numerous sites for regulation of cytokine and cytokine receptor genes by these transcription factors are found in their promoter regions. Many factors affect the formation and activity of AP-1 dimers (Fos and Jun heterodimers) through protein specific interactions or by the modulation of pre-existing complexes by phosphorylation. These complexes can vary markedly in their ability to stimulate gene transcription. Thus, induction of AP-1 activity is regulated by stimuli that either induce the de novo synthesis of AP-1 subunits or increase the activity of previously formed AP-1 dimers. NF-kappa B is activated by a number of agents including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), lipopolysaccharide (LPS) and viruses. NF-kappa B plays a central role in a range of immunological responses due to its ability to switch on inflammatory genes which lead to further activation of NF-kappa B is a heterodimer of proteins which vary in their ability to bind to DNA and/or to activate gene transcription. NF-kappa B activation is primarily regulated by sequestration of heterodimers within the cytoplasm as inactive complexes with inhibitory molecules (inhibitory-kappa B (I-kappa B)). Treatment of cells with inducing agents results in the phosphorylation of the I-kappa B molecule which is targeted for rapid degradation. This causes a rapid dissociation of the cytoplasmic NF-kappa B/I-kappa B complexes and allows translocation of the active NF-kappa B to the nucleus. Cross-coupling between NF-kappa B and AP-1 has been described which results in a synergistic increase in activity at both AP-1 and NF-kappa B sites. Elevation of both AP-1 and NF-kappa B, as reported in asthma, may therefore lead to far greater inflammation than would be present if either transcription factor alone were activated.
 ...
PMID:Transcription factors as activators of gene transcription: AP-1 and NF-kappa B. 920 18

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.
 ...
PMID:Increased spontaneous release of tumour necrosis factor-alpha by alveolar macrophages from wheezy infants. 927 17

The aim of this study was to determine the relative production of chemokines interleukin-8 (IL-8), regulated on activation, normal T-cell expressed and secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) by intrinsic and extrinsic asthmatics. Nine intrinsic asthmatics, 10 extrinsic asthmatics, five nonatopic and five atopic controls underwent bronchoalveolar lavage (BAL). Total BAL cells were cultured in the presence or absence of lipopolysaccharide. Chemokines were measured in BAL cell supernatants and in cell-free bronchoalveolar lavage fluid (BALF) by enzyme-linked immunoabsorbent assay (ELISA). BAL cell cytospins were stained immunohistochemically for chemokines. BAL cells from asthmatics produced more IL-8 than controls (statistically significant for extrinsic asthma). RANTES was elevated in the BAL cell supernatants of four out of nine intrinsic asthmatics as compared to nonatopic controls (not statistically significant). RANTES levels in the BAL cell supernatants of extrinsic asthmatics were all low. MCP-1 production by BAL cells was similar in all groups. Immunostaining of BAL cell cytospins showed the macrophage to be the predominant positive-staining cell type and correlated well with supernatant data. Measurement of chemokines in BALF showed significantly elevated IL-8 in intrinsic asthma compared to nonatopic controls, but no increase in extrinsic asthmatics relative to atopic control RANTES was elevated in three out of nine BALFs from intrinsic asthmatics compared with nonatopic controls (not statistically significant). MCP-1 was not elevated above control levels in BALF of either asthma group. These results suggest an up-regulation in the production of interleukin-8 and regulated on activation, normal T-cell expressed and secreted, but not monocyte chemotactic protein-1 (MCP-1), by macrophages in the bronchoalveolar lavage of asthmatic subjects. In addition, the data suggest that regulated on activation, normal T-cell, expressed and secreted, may be differentially produced by macrophages in atopic and nonatopic asthma.
 ...
PMID:Production of interleukin-8, RANTES and MCP-1 in intrinsic and extrinsic asthmatics. 931 10

Bronchopulmonary hyperresponsiveness (BHR) is a hallmark of asthma and other inflammatory diseases of the airways. Animal models of BHR are available in which systemic or local immunizations, followed by acute allergenic provocations into the airways, augment responses to intravenous or intratracheal nonspecific bronchoconstrictor agents. Guinea-pig models are easy to manipulate but have serious handicaps: lack of proper genetics, lack of biomolecular tools, and frequent excess of eosinophils in the bronchoalveolar lavage fluid (BALF). Murine models have proper genetics and molecular tools, and they have the further advantage of being widely used for the study of other pathologies. In many of these studies, interleukin (IL)-5 appears as a major cytokine, produced by Th2 lymphocytes. Interleukin-5 promotes eosinophil differentiation and maturation, recruitment to the airways, and possibly activation. The presence of eosinophils in the airways and in the BALF may be necessary but is not sufficient to support BHR, since intense eosinophilia may be present in its absence. Bronchopulmonary hyperresponsiveness is also induced by the administration of lipopolysaccharide (LPS); in that case, eosinophils are not involved, and the role of neutrophils and of tumor necrosis factor-alpha, even though likely, has not been proven. Comparison of BHR induced by allergen (Th2- and largely eosinophil-dependent) and by LPS (probably macrophage-dependent) should allow for a better understanding of the mechanisms of BHR and for the development of important remedies.
 ...
PMID:Modifications of experimental bronchopulmonary hyperresponsiveness. 935 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>