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)

To determine the immunological mechanisms associated with outgrowing mite antigen-induced bronchial asthma during adolescence, we studied the relationship between clinical status and Dermatophagoides farinae (Df) antigen-induced peripheral cell activation by measuring IL-1alpha and IL-1beta production in patients with bronchial asthma. After antigen-driven restimulation in vitro, there was increased IL-1alpha, IL-1beta production by peripheral blood mononuclear cells (PBMC) from patients with active bronchial asthma, while cellular IL-1alpha, IL-1beta production was reduced in patients with asthma in remission. IL-1alpha and IL-1beta production by PBMC (possibly reflecting airway inflammation) after exposure to Df antigen might be down-regulated in patients outgrowing mite antigen-induced asthma, because lipopolysaccharide-induced IL-1alpha, IL-1beta production (seen in both normal individuals and patients with active asthma) was also reduced when patients were in remission.
 ...
PMID:Reduced IL-1 production in adolescents with mite antigen asthma in remission. 969 77

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

Inducible nitric oxide (NO) synthase (iNOS)-mediated hyperproduction of NO in airways has been reported in asthmatic patients. However, the role of NO in the pathogenesis of asthma has not yet been fully elucidated. The aim of this study was to examine whether the iNOS-derived NO affects airway microvascular leakage, one of the characteristic features of asthmatic airway inflammation. Guinea-pigs were exposed to lipopolysaccharide (LPS) (1 mg x mL(-1)) by inhalation in order to induce iNOS in the airways, and the histochemical staining of reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase activity was determined 5 h after the inhalation to confirm the iNOS induction. Airway microvascular leakage to subthreshold doses of substance P (0.3 microg x kg(-1), i.v.) was also examined in the absence and presence of an iNOS inhibitor (aminoguanidine) in LPS- or saline-exposed (control) animals using Evans blue dye and Monastral blue dye. In the LPS-exposed animals, increased NADPH-diaphorase activity was observed in the airway microvasculature compared with the control animals. Substance P caused significant airway microvascular leakage assessed by Evans blue dye in all airway levels in the LPS-exposed animals but not in the control group. This was also confirmed by Monastral blue dye extravasation. Aminoguanidine abolished this LPS-induced enhancement of plasma leakage to substance P without changing the systemic blood pressure. These results may suggest that inducible nitric oxide synthase-derived nitric oxide is capable of potentiating neurogenic plasma leakage in airways.
 ...
PMID:Induction of nitric oxide synthase by lipopolysaccharide inhalation enhances substance P-induced microvascular leakage in guinea-pigs. 981 54

Inflammation in asthma is characterized by a Th2 response. In many experimental systems, this response can be regulated by interleukin (IL)-10 and IL-12. IL-10 deactivates T cells, and IL-12 reorients the response toward a Th1 pattern. Alveolar macrophages (AM) can secrete both of these cytokines, and thus regulate T-cell behavior in asthma. They can enhance the Th2 response by turning off their secretion of IL-10 and IL-12, or tend to downregulate it by producing these cytokines. To elucidate that point, we assayed the AM IL-10 and IL-12 from 11 asthmatic patients and four controls. Six asthmatics were treated by inhaled corticosteroids. AM were recovered by bronchoalveolar lavage (BAL). They were isolated and cultured for 24 h without stimulation or in the presence of lipopolysaccharide (LPS). IL-10 and the p40 subunit of IL-12 were assayed in the BAL fluid and in AM culture supernatants by ELISA. Spontaneous AM IL-10 production was higher in asthmatics, particularly in the treated group. The AM IL-10 production after stimulation by LPS was also elevated in asthmatics, but was mainly so in untreated patients. IL-12 levels were higher in BAL fluids from untreated patients than from controls. The IL-12 production of LPS-stimulated-AM from these patients was increased. These results show that AM are at least primed for the production of IL-10 and IL-12 in asthma, and suggest that these cells could be involved in the resolution of the asthmatic inflammation.
 ...
PMID:Alveolar macrophage interleukin (IL)-10 and IL-12 production in atopic asthma. 986 Feb 44

It is very surprising that in recent decades, the bacterial infection factor has been so overlooked in the causal treatment of bronchial asthma. Emphasis is put in the viral infection, but the bacterial infection usually associated with it is ignored. In several publications, we have insisted on the importance of the bacterial infection factor in the etiopathogenesis of bronchial asthma. It is alarming that even in the international consensus on its treatment this aspect is overlooked. In the first decades of this century, great importance had already been put on bacterial infection in the triggering of bronchospasm. In this review, we insist on this role of bacterial infection, which comes as a result of our extensive experience in this area, and the fact that in the last 10 years many authors have proven its responsibility at a bronchial mucosa level. In due time, we may be able to prove that the bacterial antigens can potentiate the action of inhalant allergens. Some authors have even proven that the action of these bacterial antigens even more energetically increases the number of intraepithelial dendritic cells in the bronchial mucosa after inhalation of bacterial lipopolysaccharide. Bystander respiratory bacterial infections can also directly modulate T helper 1 and 2 selection parallel to the immune response to inhalant allergens. Recent studies have also proven that in respiratory infection, bacterial antigens hold the main responsibility in the inflammatory and bronchospastic response in the etiopathogenesis of bronchial asthma. Therefore, a consequent treatment of the infection is required, by means of wide spectrum antibiotics, as well as prescription of bacterial immunotherapy, as we have emphasized on other occasions. In conclusion, we must try to cure asthmatic patients and not to maintain them with inhalers and unnecessary corticosteroid therapy, since increasing reactions to corticosteroids are witnessed every day.
 ...
PMID:Bacterial infection as an important triggering factor in bronchial asthma. 1021 51

Glucocorticosteroids (GCS) have been used successfully in the treatment of inflammatory conditions such as asthma and acute graft-vs-host disease, but their mode of action remains unclear. There have been numerous reports of the in-vitro suppression of cytokine production by GCS based on quantitation of cytokines by ELISA on bulk supernatants from isolated cell culture systems. We report the use of a whole-blood intracellular cytokine assay which is more representative of an in-vivo environment. We examined the effects of GCS, prednisolone and dexamethasone, on cytokine production by individual cells (monocytes, T lymphocytes and natural killer or NK cells) in heterogenous cell populations. Cells in whole blood were activated with various stimuli: phorbol ester and calcium ionophore for T cells, Escherichia coli lipopolysaccharide (LPS) for monocytes, and phytohaemagglutinin (PHA) plus interleukin (IL)-12 for NK cells. Brefeldin A was used as an intracellular transport inhibitor to enhance the detection of intracellular cytokine production. The effects of various concentrations (10-5, 10-7, 10-9 and 10-11 m) of GCS on cytokine production were studied using multiparameter flow cytometry. After surface staining with fluorescently-conjugated monoclonal antibodies (MoAbs) to identify cell type, cells were fixed and permeabilised. Intracellular cytokines interferon (IFN)-gamma, IL-10, IL-1alpha and beta, IL-2, tumour necrosis factor (TNF)-alpha, and IL-12 were stained with their respective conjugated MoAbs. The GCS both caused a dose-dependent modulation of cytokine production by T cells, monocytes and NK cells. After 4 h, a decrease in the MFI (amount of cytokine produced per cell) was noted for all cell types. After 24 h a decrease in both MFI and the percentage of cells producing cytokine was observed for all cell types. The exception was monocyte production of IL-10 which was enhanced at low concentrations of GCS (10-9 and 10-11 m). Our findings thus suggest that one anti-inflammatory mechanism of GCS action may be through inhibition of the release of pro-inflammatory cytokines IL-1alpha and beta, IL-2, IFN-gamma and TNF-alpha, and up-regulation of the anti-inflammatory cytokine IL-10.
 ...
PMID:Methyl-prednisolone up-regulates monocyte interleukin-10 production in stimulated whole blood. 1032 Jun 49

To examine whether the development of hard metal (HM)-induced occupational asthma and interstitial lung disease involves alterations in nitric oxide (NO) pathways, we examined the effects of an industrial HM mixture on NO production, interactions between HM and lipopolysaccharide (LPS) on NO pathways, and alterations in airway reactivity to methacholine in rat lungs. HM (2.5 to 5 mg/100 g intratracheal) increased NO synthase (NOS; EC 1.14.23) activity of rat lungs at 24 h without increasing inducible NOS (iNOS) or endothelial NOS (eNOS) mRNA abundance or iNOS, eNOS, or brain NOS (bNOS) proteins. The increase in NOS activity correlated with the appearance histologically of nitrotyrosine immunofluorescence in polymorphonuclear leukocytes (PMN) and macrophages. Intraperitoneal injection of LPS (1 mg/kg) caused up-regulation of iNOS activity, mRNA, and protein at 8 h but not at 24 h. HM at 2.5 mg/100 g, but not at 5 mg/100 g, potentiated the LPS-induced increase in NOS activity, iNOS mRNA, and protein. However, HM decreased eNOS activity at 8 h and eNOS protein at 24 h. Whole body plethysmography on conscious animals revealed that HM caused basal airway obstruction and a marked hyporeactivity to inhaled methacholine by 6-8 h, which intensified over 30-32 h. HM-treatment caused protein leakage into the alveolar space, and edema, fibrin formation, and an increase in the number of inflammatory cells in the lungs and in the bronchoalveolar lavage. These results suggest that a HM-induced increase in NO production by pulmonary inflammatory cells is associated with pulmonary airflow abnormalities in rat lungs.
 ...
PMID:Effects of hard metal on nitric oxide pathways and airway reactivity to methacholine in rat lungs. 1037 2

Individuals exposed to inhaled endotoxin (lipopolysaccharide [LPS]) can develop airway symptomatology and exacerbations of asthma. Moreover, among those occupationally exposed to organic dusts, the progression of airflow obstruction is related to the endotoxin concentration in the bioaerosol. Not everyone exposed to high concentrations of LPS develops these problems. To determine whether individuals express a differential response to inhaled LPS, we challenged 72 healthy volunteers with increasing doses of LPS. Airflow was assessed after each dose and the protocol was terminated for decline in FEV1 >/= 20%. Marked differences in the response to inhaled LPS were observed: eight "sensitive" subjects had at least 20% decline in their FEV1 after inhaling 6.5 micrograms or less of LPS, whereas 11 "hyporesponsive" subjects maintained an FEV1 >/= 90% of their baseline even after inhaling 41.5 micrograms of LPS. Serial testing demonstrated that the response to inhaled LPS is reproducible. Sensitive subjects were more commonly female and hyporesponsive subjects were more often male (p = 0.016). Peripheral blood monocytes from hyporesponsive subjects, compared with sensitive subjects, released less interleukin (IL)-6 and IL-8. These findings demonstrate that an LPS phenotype can be reproducibly elicited in humans, which creates an opportunity to identify genes involved in this response to inhaled LPS.
 ...
PMID:Variable airway responsiveness to inhaled lipopolysaccharide. 1039 Apr 15

Eosinophil-derived cationic proteins play an essential role in the pathogenesis of bronchial asthma. We tested whether cationic proteins interfere with the cationic amino-acid transport in alveolar macrophages (AMPhi) and tracheal epithelial cells, and whether L-arginine-dependent pathways were affected. The effect of cationic polypeptides on cellular uptake of [(3)H]-L-arginine, nitrite accumulation, and the turnover of [(3)H]-L-arginine by nitric oxide (NO) synthase and arginase (formation of [(3)H]-L-citrulline and [(3)H]-L-ornithine, respectively) were studied. Poly-L-arginine reduced [(3)H]-L-arginine uptake in rat AMPhi and tracheal epithelial cells in a concentration-dependent manner (at 300 microgram/ml by 70%). Poly-L-lysine, protamine, and major basic protein (each up to 300 microgram/ml) tested in rat AMPhi inhibited [(3)H]-L-arginine uptake by 35 to 50%. During 6 h incubation in amino acid-free Krebs solution, rat AMPhi, precultured in the absence or presence of LPS (1 microgram/ml), accumulated 1.4 and 3.5 nmol/10(6) cells nitrite, respectively. Addition of 100 microM L-arginine increased nitrite accumulation by 70 and 400% in control and lipopolysaccharide-treated AMPhi, respectively. Nitrite accumulation in the presence of L-arginine was reduced by poly-L-arginine and poly-L-lysine (100 and 300 microgram/ml) by 60 to 85% and 20 to 30%, respectively. Poly-L-arginine, but not poly-L-lysine, inhibited nitrite accumulation already in the absence of extracellular L-arginine. Poly-L-arginine (300 microgram/ml) inhibited [(3)H]-L-citrulline formation by AMPhi stronger than that of [(3)H]-L-ornithine. We conclude that cationic proteins can inhibit cellular transport of L-arginine and this can limit NO synthesis. Poly-L-arginine inhibits L-arginine uptake more effectively than other cationic proteins and exerts additional direct inhibitory effects on NO synthesis.
 ...
PMID:Cationic proteins inhibit L-arginine uptake in rat alveolar macrophages and tracheal epithelial cells. Implications for nitric oxide synthesis. 1042 96

Glucocorticoids are potent anti-inflammatory agents capable of influencing cytokine release in a number of cell types. The aim of the present study was to investigate whether glucocorticoids, frequently used in the treatment of asthma, interfere with cytokine secretion by lung epithelial cells and alveolar macrophages in vitro. Inhalation of swine dust induces airway inflammation with influx of inflammatory cells and release of proinflammatory cytokines in the lungs. Therefore, human lung epithelial cells (A549) and human alveolar macrophages were stimulated with swine dust or lipopolysaccharide (LPS), and the inhibitory effect of budesonide and fluticasone propionate on cytokine release was studied in a dose-response (10(-13)-10(-8) M) manner. The time course for the steroid effect was also investigated. Both steroids caused a dose-dependent, almost total, inhibition of swine dust-induced IL-6 and IL-8 release from epithelial cells and LPS-induced IL-6 and TNF-alpha from alveolar macrophages. The steroids only partially inhibited IL-8 release from alveolar macrophages. Budesonide was approximately 10 times less potent than fluticasone propionate. Preincubation with the steroids did not inhibit cytokine release more than simultaneous incubation with stimulus and steroid. In conclusion, budesonide and fluticasone propionate, in concentrations that probably occur in the airway lining fluid during inhalational therapy, inhibited cytokine release from human lung epithelial cells (IL-6, IL-8) and alveolar macrophages (TNF-alpha, IL-6, IL-8). In vitro, the onset of this effect was rapid.
 ...
PMID:Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages. 1044 24


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