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)

Helicobacter pylori plays a major role in the pathogenesis of gastric disease. The gastric epithelial integrity is compromised by the H. pylori cell wall lipopolysaccharide untoward effect on the gastric epithelial cell receptors interaction with proteins of extracellular matrix, glycoproteins of mucus coat, and bioactive peptides. These interactions cause the weakening of the mucus coat rendering the underying epithelium vulnerable to noxious luminal contents and disrupting the regulatory feedback of somatostatin and gastrin. Moreover, H. pylori lipopolysaccharide induces histologic lesions typical of acute gastritis and these changes are reflected in the increased epithelial cell apoptosis. These findings thus identify cell wall lipopolysaccharide as a virulent factor responsible for the H. pylori effect on gastric epithelium. The effect of antiulcer agents on the interference of lipopolysaccharide with the laminin receptor was found to be most efficiently countered by ebrotidine, sulglycotide and sucralfate, whereas sulglycotide is the most potent in the reversal of the inhibitory effect of the lipopolysaccharide on mucin receptor binding. In the case of somatostatin-receptor binding, sulglycotide followed by sucralfate and ebrotidine showed the most potency in of reversing the effect of H. pylori lipopolysaccharide. Thus these antiulcer agents have a great promise in the treatment gastric diseases associated with H. pylori infection.
 ...
PMID:Lipopolysaccharide a virulence factor of Helicobacter pylori: effect of antiulcer agents. 959 7

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.
 ...
PMID:Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria. 963 Jun 59

We recently described a murine model of atopic asthma in which a marked, extensive hyperplasia of airway goblet cells is induced by repeated challenge of ovalbumin (OA)-sensitized mice with intratracheally administered allergen (Am. J. Respir. Cell Mol. Biol. 1996;14:425-438). We report here the time course of the duration of this feature and of its spontaneous resolution in the absence of further allergen exposure. Induction of severe neutrophilic inflammation in the airways by repeated intratracheal administration of lipopolysaccharide failed to induce goblet cell hyperplasia (GCH) to as great a degree as that induced by allergen, suggesting that nonallergic inflammation is a relatively poor inducer of this phenotype change in mice. When a "subclinical" infection of the lungs with the human A2 strain of respiratory syncytial virus was superimposed on the model of atopic asthma, recruitment of monocytes and lymphocytes to the airways was enhanced and a discharge of goblet cell mucin contents was observed. This may partly explain the respiratory difficulty that typifies virally induced exacerbations of asthma in humans. Daily systemic treatment of sensitized mice with dexamethasone during the period of allergen challenge produced a dose-related suppression of developing GCH, while similar treatment during the period following the establishment of extensive hyperplasia induced an accelerated resolution toward a normal epithelial phenotype. These results confirm and extend the relevance of this model as a representation of the human disease.
 ...
PMID:Induction, duration, and resolution of airway goblet cell hyperplasia in a murine model of atopic asthma: effect of concurrent infection with respiratory syncytial virus and response to dexamethasone. 965 Nov 79

Fractalkine is distinguished structurally from other chemokines in that it contains a mucin-like stalk that tethers a CX3C chemokine module to a transmembrane-spanning region; its expression in cultured endothelial cells has been shown to be up-regulated by tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1). The purpose of this study was to determine whether fractalkine is expressed, in a proinflammatory agent-regulated manner, by cardiac endothelial cells in vivo. Steady state levels of fractalkine mRNA were increased in rat cardiac tissues after in vivo treatment with lipopolysaccharide (LPS), IL-1, or TNF-alpha. In situ hybridization and immunohistochemical analysis revealed that endothelial cells of the coronary vasculature and endocardium were the principal source of proinflammatory agent-inducible fractalkine, although some fractalkine immunoreactivity was also found on the myocytes. These data are the first demonstration of in vivo cardiac endothelial cell fractalkine expression and regulation by proinflammatory agents such as LPS, IL-1, or TNF-alpha. Cardiac endothelial cell-expressed fractalkine may contribute to the influx of leukocytes into the heart during inflammation.
 ...
PMID:Inflammatory agents regulate in vivo expression of fractalkine in endothelial cells of the rat heart. 1061 75

Environmental toxins, infection, and allergens lead to a transient mucous cell hyperplasia (MCH) in airway epithelia; however, the mechanisms for reducing mucous cell numbers during recovery are largely unknown. This study investigated Bcl-2 expression in mucous cells induced by a neutrophilic or eosinophilic inflammatory response. Brown Norway rats intratracheally instilled with lipopolysaccharide (LPS) showed an inflammatory response characterized primarily by neutrophils. Secreted mucin was increased fourfold at 1 day, and the number of mucous cells was increased fivefold 2, 3, and 4 days post-LPS instillation compared with those in noninstilled rats. None of the mucous cells in non- or saline-instilled control animals expressed Bcl-2, whereas 20-30% of mucous cells were Bcl-2 positive 1 and 2 days post-LPS instillation. Brown Norway rats immunized and challenged with ovalbumin (OVA) for 2, 4, and 6 days showed an inflammatory response characterized primarily by eosinophils. Secreted mucin increased fivefold, and mucous cell number increased fivefold after 4 and 6 days of OVA exposure compared with water-immunized control rats challenged with OVA aerosols. Approximately 10-25% of mucous cells were Bcl-2 positive in OVA-immunized and -challenged rats. These data demonstrate Bcl-2 expression in hyperplastic mucous cells of Brown Norway rats regardless of the type of inflammatory response and indicate that apoptotic mechanisms may be involved in the resolution of MCHs.
 ...
PMID:Bcl-2 in LPS- and allergen-induced hyperplastic mucous cells in airway epithelia of Brown Norway rats. 1107 11

A murine model of lipopolysaccharide (LPS)-induced airway inflammation and epithelial cell phenotypic change, and the time courses of these events are described. A single intratracheal instillation of Pseudomonas aeruginosa LPS in mice resulted in massive recruitment of neutrophils to the lung 2 d after treatment as assessed by differential cell counts of the inflammatory cells in bronchoalveolar lavage fluid and histologic assessment of hematoxylin and eosin (H&E)-stained lung sections. The LPS-induced neutrophilic inflammation subsided substantially on Day 4 and essentially vanished by Day 7. Airway epithelial mucus cells were not detected by Alcian blue periodic acid-Schiff staining until Day 4 after LPS treatment and became more abundant in number as well as in mucus content on Day 7. The expression of Muc5ac messenger RNA (mRNA) as well as glycoprotein was enhanced on Day 2, peaked on Day 4, and decreased on Day 7, whereas enhanced expression of mucin core 2 beta6 N-acetylglucosaminyltransferase (C2GnT)-M mRNA was not detected until Day 4 and peaked on Day 7. The expression of C2GnT-L mRNA in the lung, a marker for activated leukocytes as well as mucus cells, peaked on Day 2 and remained moderately high until Day 7. C2GnT-L mRNA expression in LPS-treated lung correlated with the presence of neutrophils and the appearance of mucus cells in the airway epithelium. We conclude that mucus cell metaplasia and hyperplasia can be generated in mouse lungs with a single intratracheal instillation of LPS. In addition, C2GnT-M may serve as a marker for mucus cells in mouse lung. This LPS-induced mucus cell metaplasia and hyperplasia model should be useful for the study of Pseudomonas-induced airway mucus hypersecretory diseases.
 ...
PMID:Lipopolysaccharide Induces Mucus Cell Metaplasia in Mouse Lung. 1115 52

To examine the differential properties of mucous glycoproteins, we produced hypertrophic and metaplastic changes in goblet cells of rat nasal epithelium by intranasal instillation of ovalbumin (OVA) in OVA-sensitized rats, and by intranasal lipopolysaccharide (LPS) instillation. The epithelial mucosubstance was quantitatively examined by alcian blue-periodic acid-Schiff (AB-PAS) and lectin histochemistry. The newly produced mucin after OVA challenge or LPS instillation contained a high amount of sulfomucin and a low amount of neutral glycoprotein: LPS-induced mucin contained more sulfomucin (70.1% of total) and less neutral glycoprotein (8.6%) than OVA-induced mucin (sulfomucin, 33.6%; neutral glycoprotein, 41.8%; p < 0.01). Four of the lectins stained some of the mucosubstance, indicating the presence of galactose-N-acetylgalactosamine, alpha2,3- and alpha2,6-linked sialic acid-galactose, and fucose residues. After LPS instillation, the reactivity was higher for galactose-N-acetylgalactosamine (64.8% of total) and alpha2,3-linked sialic acid-galactose (75.8%) than after saline instillation (3.5 and 19.1%, respectively) or OVA challenge (5.8 and 32.3%; p < 0.05). OVA challenge did not induce the alteration of terminal sugar residues. A 2-fold increase in mucin mRNA (rat Muc5ac) expression was induced after LPS instillation or OVA challenge, compared with animals treated with saline instillation (p < 0.05). These results indicate that mucin mRNA expression (for peptide backbone) increases similarly after LPS instillation or OVA challenge; however, carbohydrate compositions of newly produced mucin are different between the two groups.
 ...
PMID:Differential properties of mucous glycoproteins in rat nasal epithelium. A comparison between allergic inflammation and lipopolysaccharide stimulation. 1158

Helicobacter pylori is a primary factor in the etiology of gastric disease, and its early pathogenic effects are manifested by up-regulation of inflammatory processes and the loss of mucus coat continuity. We investigated the role of extracellular signal-regulated kinase (ERK) and p38 mitogen activated protein kinase (MAPK) in the disturbances in gastric mucin synthesis and apoptotic processes evoked by H. pylori lipopolysaccharide (LPS). Exposure of gastric mucosal cells to the LPS led to a dose-dependent decrease (up to 59.5%) in mucin synthesis, accompanied by a marked increase in caspase-3 activity and apoptosis. Inhibition of ERK with PD98059 accelerated (up to 36.1%) the LPS-induced decrease in mucin synthesis, and caused further enhancement in caspase-3 activity and apoptosis. Blockade of p38 kinase with SB203580 produced reversal in the LPS-induced reduction in mucin synthesis, and substantially countered the LPS-induced increases in caspas-3 activity and apoptosis. Moreover, inhibition of caspase-3 blocked the LPS-induced increase in caspse-3 activity and produced an increase in mucin synthesis. Thus the detrimental influence of H. pylori LPS on gastric mucin synthesis is closely linked to caspase-3 activation and apoptosis, and involves ERK and p38 kinase participation.
 ...
PMID:Disruption in gastric mucin synthesis by Helicobacter pylori lipopolysaccharide involves ERK and p38 mitogen-activated protein kinase participation. 1205 97

The respiratory epithelium provides both a physical and an immunological barrier to inhaled pathogens. In the normal host, innate defences prevent bacteria from activating inflammation by providing efficient muco-ciliary clearance and antimicrobial activity. Bacteria that persist in the airway lumen, as in cystic fibrosis, activate both the professional immune cells in the respiratory mucosa as well as the more abundant airway epithelial cells. As most of the bacteria become entrapped in airway mucin, shed bacterial products such as pili, flagella, peptidoglycan and lipopolysaccharide from lysed bacteria are likely to be the stimuli most important in activating epithelial signalling. The airway cells respond briskly to bacterial components through several signalling systems which activate epithelial expression of pro-inflammatory cytokines and chemokines. These signals recruit neutrophils to the airways where they eliminate the contaminating bacteria causing inflammation and the ensuing clinical signs of infection.
 ...
PMID:Host-bacterial interactions in the initiation of inflammation. 1205 26

To address the complex chronic effector properties of interleukin (IL)-10, we generated transgenic mice in which IL-10 was overexpressed in the lung. In these mice, IL-10 inhibited endotoxin-induced tumor necrosis factor production and neutrophil accumulation. IL-10 also caused mucus metaplasia, B and T cell-rich inflammation, and subepithelial fibrosis and augmented the levels of mRNA encoding Gob-5, mucins, and IL-13. In mice bred to have null mutations of IL-13, IL-4R(alpha), or STAT-6, transgenic IL-10 did not induce mucus metaplasia but did induce inflammation and fibrosis. IL-10 was also a critical mucin regulator of virus-induced mucus metaplasia. Thus, IL-10, although inhibiting lipopolysaccharide-induced inflammation, also causes mucus metaplasia, tissue inflammation, and airway fibrosis. These responses are mediated by multiple mechanisms with mucus metaplasia being dependent on and the inflammation and fibrosis being independent of an IL-13/IL-4R(alpha)/STAT-6 activation pathway.
 ...
PMID:Transgenic overexpression of interleukin (IL)-10 in the lung causes mucus metaplasia, tissue inflammation, and airway remodeling via IL-13-dependent and -independent pathways. 1210 90


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