UNIPROT:P43026 - FACTA Search

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)

Platelet -activating factor (PAF), a phospholipid-derived messenger molecule, is now recognized as the most proximal mediator of cellular events triggered by bacterial lipopolysaccharide (LPS) stimulation. In this study, we assessed the role of PAF in the disturbances in salivary mucin synthesis evoked by LPS of periodontopathic bacterium, P. gingivalis. Using primary culture of mucous acinar cells of sublingual salivary gland, we show that a specific PAF antagonist, BN52020, prevents in a dose-dependent fashion (up to 83.7%) the LPS-induced reduction in mucin synthesis, and the effect is reflected in a marked decrease in the LPS-induced apoptosis (74.8%), NO generation (82.6%), and the expression of TNF-alpha (76.1%). The impedance by BN52020 of the LPS inhibitory effect on mucin synthesis was blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), which also obviated the inhibitory effect of BN52020 on the LPS-induced upregulation in apoptosis, TNF-alpha, and NO. A potentiation in the impedance by BN52020 of the LPS detrimental effect on mucin synthesis was however attained with NOS-2 inhibitor, 1400W, while cNOS inhibitor, L-NNA caused a reduction in the impedance effect of BN52020. However, while 1400W and BN52020 countered the potentiating effect of wortmannin on the LPS-induced decrease in mucin synthesis, a further exacerbation of the effect of wortmannin occurred in the presence of L-NNA. The findings implicate PAF as a pivotal factor affecting the extent of pathological consequences of P. gingivalis infection on salivary glands capacity for mucin production, and suggest that its release in response to the LPS serves as a negative regulator of PI3K controlling the pathway of cNOS activation.
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PMID:Platelet-activating factor mediates Porphyromonas gingivalis lipopolysaccharide interference with salivary mucin synthesis via phosphatidylinositol 3-kinase-dependent constitutive nitric-oxide synthase activation. 1508 69

Peroxisome proliferator-activated receptor gamma (PPARgamma) has emerged recently as an important participant in the resolution of inflammation by conveying signals that lead to mitogen-activated protein kinase (MAPK) cascade activation. In this study, we report that PPARgamma activation leading to the impedance of P. gingivalis lipopolysaccharide (LPS) inhibitory effect on salivary mucin synthesis requires epidermal growth factor receptor (EGFR) participation. We show that activation of PPARgamma with a specific agonist, ciglitazone, prevents the LPS-induced reduction in mucin synthesis, and the effect is reflected in a marked decrease in apoptosis, caspase-3 activity and NO generation. The impedance by ciglitazone of the LPS-induced reduction in mucin synthesis was countered (up to 68.9%) in a dose-dependent fashion by a specific inhibitor of EGFR kinase, PD153035, as well as wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K). Moreover, the inhibitory effect of ciglitazone on the LPS-induced reduction in mucin synthesis and upregulation in apoptosis, caspase-3 activity, and NO generation was blunted by a selective inhibitor of tyrosine kinase Src, PP2, responsible for ligand-independent EGFR transactivation. These findings indicate that PPARgamma activation leading to the suppression of P. gingivalis LPS inhibition of salivary mucin synthesis involves Src kinase-dependent EGFR transactivation.
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PMID:Src kinase-dependent epidermal growth factor receptor transactivation in PPARgamma ligand-induced suppression of Porphyromonas gingivalis interference with salivary mucin synthesis. 1518 49

Peroxisome-proliferator-activated receptor gamma (PPARgamma) is recognized for its role in regulation of genes associated with inflammation, and its activation of phosphatidylinositol 3-kinase (PI3K) has emerged recently as an important regulator of mucosal responses to bacterial infection. In this study, we report that PPARgamma activation leading to the impedance of Helicobacter pylori lipopolysaccharide (LPS) inhibitory effect on salivary mucin synthesis requires epidermal growth factor receptor (EGFR) participation. Using gastric mucosal cells in culture, we show that activation of PPARgamma with a specific agonist, ciglitazone, prevents the LPS-induced reduction in mucin synthesis, and the effect is reflected in a marked decrease in apoptosis, caspase-3 activity and NO generation. The impedance by ciglitazone of the LPS-induced reduction in mucin synthesis was blunted (up to 65.8%) in a concentration-dependent fashion by a specific inhibitor of EGFR kinase, PD153035, as well as the PPARgamma antagonist BADGE, and wortmannin, an inhibitor of PI3K. Moreover, the inhibitory effect of ciglitazone on the LPS-induced reduction in mucin synthesis and upregulation in apoptosis, caspase-3 activity and NO generation was countered by PP2, a selective inhibitor of tyrosine kinase Src responsible for ligand-independent EGFR transactivation. These findings indicate that PPARgamma activation leading to the suppression of H. pylori LPS inhibition of gastric mucin synthesis involves Src kinase-dependent EGFR transactivation.
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PMID:Role of epidermal growth factor receptor transactivation in PPAR gamma-dependent suppression of Helicobacter pylori interference with gastric mucin synthesis. 1526 18

We reported recently that interleukin (IL)-1beta exposure resulted in a prolonged increase in MUC5AC mucin production in normal, well differentiated, human tracheobronchial epithelial (NHTBE) cell cultures, without significantly increasing MUC5AC mRNA (Am J Physiol 286:L320-L330, 2004). The goal of the present study was to elucidate the signaling pathways involved in IL-1beta-induced MUC5AC production. We found that IL-1beta increased cyclooxygenase-2 (COX-2) mRNA expression and prostaglandin (PG) E(2) production and that the COX-2 inhibitor celecoxib suppressed IL-1beta-induced MUC5AC production. Addition of exogenous PGE(2) to NHTBE cultures also increased MUC5AC production and IL-1beta-induced Muc5ac hypersecretion in tracheas from wild-type but not from COX-2-/- mice. NHTBE cells expressed all four E-prostanoid (EP) receptor subtypes and misoprostol, an EP2 and EP4 agonist, increased MUC5AC production, whereas sulprostone, an EP1 and EP3 agonist, did not. Furthermore, specific protein kinase A (PKA) inhibitors blocked IL-1beta and PGE(2)-induced MUC5AC production. However, neither inhibition of epidermal growth factor receptor (EGFR) activation with the tyrosine kinase inhibitor 4-(3-chloroanilino)-6,7-dimethoxyquinazoline HCl (AG-1478) or EGFR blocking antibody nor inhibition of extracellular signal-regulated kinase/P-38 mitogen activated protein kinases with specific inhibitors blocked IL-1beta stimulation of MUC5AC mucin production. We also observed that tumor necrosis factor (TNF)-alpha, platelet activating factor (PAF), and lipopolysaccharide (LPS) induced COX-2 and increased MUC5AC production that was blocked by celecoxib, suggesting a common signaling pathway of inflammatory mediator-induced MUC5AC production in NHTBE cells. We conclude that the induction of MUC5AC by IL-1beta, TNF-alpha, PAF, and LPS involves COX-2- generated PGE(2), activation of EP2 and/or EP4 receptor(s), and cAMP-PKA-mediated signaling.
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PMID:Interleukin-1beta-induced mucin production in human airway epithelium is mediated by cyclooxygenase-2, prostaglandin E2 receptors, and cyclic AMP-protein kinase A signaling. 1526 25

The respiratory epithelium plays a major role in the primary defense of the airways against infection. It has been demonstrated that bacterial products are involved in the induction of inflammatory reactions of the upper airways. Little is known about the effects of bacterial products on expression of the antimicrobial peptide hCAP-18/LL-37, the only human cathelicidin identified so far. The aim of this study was to investigate the effects of bacterial products from both gram-positive and gram-negative bacteria on the expression of hCAP-18/LL-37 by sinus epithelial cells using an air-exposed tissue culture model. Lipopolysaccharide and lipoteichoic acid both increased hCAP-18/LL-37 expression in cultured sinus epithelium as assessed by immunohistochemistry, where maximal stimulation occurred at 100 ng ml(-1) lipopolysaccharide or 10 microg ml(-1) lipoteichoic acid. The stimulatory effect of lipopolysaccharide and lipoteichoic acid was not restricted to expression of hCAP-18/LL-37, since also mucin expression and IL-8 release from cultured sinus epithelium cells were increased by lipopolysaccharide and lipoteichoic acid. This suggests that bacterial products may stimulate innate immunity in the upper airways.
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PMID:Bacterial products increase expression of the human cathelicidin hCAP-18/LL-37 in cultured human sinus epithelial cells. 1536 8

Endothelin-I (ET-1) is a 21 amino acid peptide produced from a biologically inactive big ET-1 by the action of endothelin-converting enzyme-1 (ECE-1) that acts through G protein-coupled ETA and ETB receptors. Using mucous cells of sublingual salivary gland, we show that P. gingivalis lipopolysaccharide (LPS) inhibitory effect on salivary mucin synthesis is accompanied by a marked increase in ET-I generation and the enhancement in ECE-1 activity. Inhibition of ECE-I with phosphoramidon led to the impedance of the LPS-induced ET-1 generation as well as countered the detrimental effect of the LPS on mucin synthesis. Moreover, the LPS inhibitory effect of on mucin synthesis was blocked by ETA receptor antagonist, BQ610, but not by ETB receptor antagonist, BQ788. The LPS-induced reduction in mucin synthesis, furthermore, was countered by PD153035 (76.8%), a specific inhibitor of EGFR kinase as well as PP2 (54.7%), a selective inhibitor of tyrosine kinase Src responsible for ligand-independent EGFR transactivation. Our findings are the first to demonstrate that P. gingivalis LPS detrimental effect on salivary mucin synthesis is intimately linked to the events controlled by EGFR transactivation, triggered by upregulation in ECE-1,enhancement in ET-1 production, and G protein-coupled ETA receptor activation.
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PMID:Porphyromonas gingivalis lipopolysaccharide-induced up-regulation in endothelin-1 interferes with salivary mucin synthesis via epidermal growth factor receptor transactivation. 1581 58

15-Deoxy-delta(12, 14)-prostaglandin J2 (15d-PG J2) is a regulator of a nuclear transcriptional factor, peroxisome proliferator-activated receptor (PPAR)-gamma. A previous study has demonstrated that 15d-PG J2 enhanced acute lung injury induced by lipopolysaccharide (LPS) in mice. 15d-PG J2 induced mucin-producing cells in the bronchial epithelium, especially in the presence of LPS. The present study investigated the effects of 15d-PG J2 on the activation of GATA-3 and Signal Transducer and Activator of Transcription (STAT) 6, important transcriptional factors in mucus secretion, in the lung in the presence or absence of LPS. ICR mice were divided into 4 experimental groups that intratracheally received vehicle, lipopolysaccharide (LPS: 125 microg/kg), 15d-PG J2 (1 mg/kg), or 15d-PG J2 + LPS. The nuclear localization of GATA-3 and phosphorylated STAT 6 was evaluated 2 h after the intratracheal administration. 15d-PG J2 enhanced the nuclear localization of GATA-3 in the presence of LPS, whereas the nuclear localization of phosphorylated STAT 6 was not altered in the groups. These results suggest that the enhancing effects of 15d-PG J2 on the production of mucin-producing cells might be related, at least in part, to the activation of GATA-3.
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PMID:Effects of 15-deoxy-delta(12,14)-prostaglandin J2 on nuclear localization of GATA-3 in the murine lung in the presence of lipopolysaccharide. 1581 89

Activation of the adenosine A(2A) receptor has been postulated as a possible treatment for lung inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). In this report, we have studied the anti-inflammatory properties of the reference A(2A) agonist CGS-21680, given intranasally at doses of 10 and 100 microg/kg, in a variety of murine models of asthma and COPD. After an acute ovalbumin challenge of sensitized mice, prophylactic administration of CGS-21680 inhibited the bronchoalveolar lavage fluid inflammatory cell influx but not the airway hyperreactivity to aerosolized methacholine. After repeated ovalbumin challenges, CGS-21680 given therapeutically inhibited the bronchoalveolar lavage fluid inflammatory cell influx but had no effect on the allergen-induced bronchoconstriction, the airway hyperreactivity, or the bronchoalveolar lavage fluid mucin levels. As a comparator, budesonide given intranasally at doses of 0.1-1 mg/kg fully inhibited all the parameters measured in the latter model. In a lipopolysaccharide-driven model, CGS-21680 had no effect on the bronchoalveolar lavage fluid inflammatory cell influx or TNF-alpha, keratinocyte chemoattractant, and macrophage inflammatory protein-2 levels, but potently inhibited neutrophil activation, as measured by bronchoalveolar lavage fluid elastase levels. With the use of a cigarette smoke model of lung inflammation, CGS-21680 did not significantly inhibit bronchoalveolar lavage fluid neutrophil infiltration but reversed the cigarette smoke-induced decrease in macrophage number. Together, these results suggest that activation of the A(2A) receptor would have a beneficial effect by inhibiting inflammatory cell influx and downregulating inflammatory cell activation in asthma and COPD, respectively.
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PMID:Effect of adenosine A2A receptor activation in murine models of respiratory disorders. 1633 80

The human MUC7 gene encodes a low-molecular-mass mucin that participates in the maintenance of healthy epithelium in the oral cavity, and possibly in respiratory tracts, by promoting the clearance of various bacteria. We examined whether MUC7 gene is expressed in primary normal human tracheobronchial epithelial cells and whether the expression is modulated by exogenous factors. By assessing MUC7 transcripts, we found that the MUC7 gene was induced by culturing the normal human tracheobronchial epithelial cells at the air-liquid interface, in which the cells were well differentiated. When the cells were treated with a panel of cytokines (IL-1beta, IL-4, IL-13, and TNF-alpha), epidermal growth factor, or a bacterial product (Pseudomonas aeruginosa lipopolysaccharide [LPS]), MUC7 transcripts and glycoprotein products were increased 1.7- to 3.2-fold. The effect of LPS on MUC7 gene expression was also studied in the airway tissues of MUC7 gene transgenic mice. In the in vitro cultured trachea and lung explants, the LPS-treated tissues showed over 2-fold increased levels of MUC7 mRNA compared with the untreated specimens. These results were confirmed by in vivo studies using the lungs and tracheas harvested from the transgenic mice irritated by LPS through the tracheal instillation. By immunohistochemistry, MUC7 glycoprotein was localized in tracheal submucosa within the serous cells. Upon LPS stimulation, the overexpressed MUC7 remains confined to the serous glands. In the lungs, MUC7 seems to be expressed within the respiratory epithelium at the level of the bronchioles. Upon stimulation with LPS, it seems to be overexpressed within the same cells and within the stromal tissue.
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PMID:Modulation of MUC7 mucin expression by exogenous factors in airway cells in vitro and in vivo. 1651 18

A natural lectin (nominated PjLec) was isolated from haemolymph of the shrimp Penaeus japonicus by affinity chromatography with fetuin-Sepharose. The result of SDS-PAGE showed that the purified PjLec protein consisted of 37kDa subunits. The native PjLec behaved as a 452kDa protein in gel filtration chromatography. Those data suggest that PjLec is composed of 12 subunits of similar molecular weight. PjLec has a broad spectrum of bacterial-agglutination activities against both Gram-positive and Gram-negative bacteria, including two Vibrio species and two other strains pathogenic for shrimp. In addition, PjLec could agglutinate all the vertebrate erythrocytes tested, and the haemagglutination was calcium-independent. The haemagglutination of PjLec was inhibited by ManNAc, Neu5A and lipopolysaccharide. Bovine submaxillary mucin, which contains mainly Neu5A, was the most potent inhibitor of PjLec (MIC of 0.0006mgml(-1)). The haemagglutination activity of PjLec was stable between pH 6 and pH 8, and was temperature-dependent. Our results suggested that PjLec may be an important humoral defence factor against bacterial infection in P. japonicus.
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PMID:Purification and characterisation of a calcium-independent lectin (PjLec) from the haemolymph of the shrimp Penaeus japonicus. 1682 70

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