Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

This study demonstrates for the first time that respiratory epithelial cells are able to produce the acute phase protein lipopolysaccharide (LPS)-binding protein (LBP), which is known to play a central role in the defense to bacterial endotoxins (or LPS). Indications for local presence of LBP in human lung was obtained via reverse transcriptase/polymerase chain reaction that showed LBP messenger RNA (mRNA) expression. Therefore, LBP production by the human lung epithelial cell line A549, a human adenocarcinoma with features of type II pneumocytes, was studied. These cells produced LBP in response to interleukin (IL)-1beta, IL-6, and tumor necrosis factor- alpha, a response that was strongly enhanced by dexamethasone. In addition, LBP mRNA was detected in A549 cells, in increasing amounts as a result of stimulation. The pattern of cytokine-induced LBP production in A549 cells was similar to the pattern in the human liver epithelial cell line HuH-7. Moreover, the molecular weight of A549-derived LBP was approximately 60 kD, which is similar to HuH-7-derived LBP. Biologic activity of LBP produced by A549 cells was evaluated on the basis of its ability to interact with LPS. Further indications that type II alveolar epithelial cells are able to produce LBP were obtained from the observations that the murine lung type II epithelial cell line C10 produced murine LBP, and that isolated human primary type II pneumocytes expressed LBP mRNA, which was enhanced after stimulation of cells. The local production of this endotoxin binding protein by lung epithelial cells might contribute to a highly specific response at the site of exposure to bacteria and bacterial endotoxins.
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PMID:Production of the acute-phase protein lipopolysaccharide-binding protein by respiratory type II epithelial cells: implications for local defense to bacterial endotoxins. 1091 79

Carbohydrates on tumor cells have been shown to play an important role in tumor metastasis. We demonstrated before that CD24, a Mr 35,000-60,000 mucine-type glycosylphosphatidylinositol-linked cell surface molecule, can function as ligand for P-selectin and that the sialylLex carbohydrate is essential for CD24-mediated rolling of tumor cells on P-selectin. To investigate the role of both antigens more closely, we transfected human A125 adenocarcinoma cells with CD24 and/or fucosyltransferase VII (Fuc TVII) cDNAs. Stable transfectants expressed CD24 and/or sialylLex. Biochemical analysis confirmed that in A125-CD24/FucTVII double transfectants, CD24 was modified with sialylLex. Only double transfectants showed rolling on P-selectin in vivo. When injected into mice, double transfectants arrested in the lungs, and this step was P-selectin dependent because it was strongly enhanced in lipopolysaccharide (LPS) pretreated wild-type mice but not in P-selectin knockout mice. CD24 modified by sialylLex was required on the tumor cells because the LPS-induced lung arrest was abolished by removal of CD24 from the cell surface by phosphatidylinositol-specific phospholipase C. A125-FucTVII single transfectants expressing sialylLex but not CD24 did not show P-selectin-mediated lung arrest. The sialylLex epitope is abundantly expressed on human carcinomas, and significant correlations between sialylLex expression and clinical prognosis exist. Our data suggest an important role for sialylLex-modified CD24 in the lung colonization of human tumors.
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PMID:The CD24/P-selectin binding pathway initiates lung arrest of human A125 adenocarcinoma cells. 1111 57

Synergistic induction of the inducible nitric oxide synthase (NOS II) gene requires a combination of interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). In this study, we determined whether the induction of IFN-gamma was required for NOS II-mediated antitumor activity in vivo. Highly metastatic H7 murine pancreatic adenocarcinoma cells were implanted into the subcutis, footpad, and pancreas of syngeneic IFN-gamma(+/+) and IFN-gamma(-/-) mice. These cells grew and produced metastases and ascites in IFN-gamma(+/+) mice. In sharp contrast, the same tumor cells grew much more aggressively, metastasized more extensively, and produced a larger amount of malignant ascites in IFN-gamma(-/-) mice. Also, induction of IFN-gamma correlated with NOS II gene expression and NO production in IFN-gamma(+/+) injected with the tumor cells but not in IFN-gamma(-/-) mice or IFN-gamma(+/+) mice without tumor challenge. In vitro, only LPS plus IFN-gamma induced a high level of NO production and cytotoxicity against H7 cells. These data suggested that the tumor cells stimulated IFN-gamma secretion from host cells, which in turn stimulated NO production by host cells and suppressed tumor growth and metastasis.
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PMID:Genetic disruption of host interferon-gamma drastically enhances the metastasis of pancreatic adenocarcinoma through impaired expression of inducible nitric oxide synthase. 1168 72

Interleukin (IL) -6 and IL-8 are cytokines that have been shown to play a role in several pancreatic diseases, including acute pancreatitis, chronic pancreatitis, and pancreatic adenocarcinoma. Previously, we have demonstrated that tumor necrosis factor-alpha (TNF-alpha) and gram-negative bacterial lipopolysaccharide stimulate production of IL-6 and IL-8 and activation of the transcription factor NF-kappaB in the well-differentiated pancreatic ductal adenocarcinoma cell lines CAPAN-1 and CAPAN-2. In these studies we have examined the effect of chain-breaking and glutathione-enhancing antioxidants on NF-kappaB activation and production of IL-6 and IL-8 in these cell lines. Generally, suppression of NF-kappaB activation correlated well with inhibition of IL-6 and IL-8 secretion. In the CAPAN-2 cell line, antioxidants inhibited both NF-kappaB activation and IL-6 and IL-8 secretion. In the CAPAN-1 cell line, antioxidants generally failed to suppress both NF-kappaB activation and IL-6 and IL-8 secretion. The single exception was the chain-breaking antioxidant butylated hydroxyanisole (BHA), which markedly inhibited IL-6 and IL-8 secretion, but had no effect on NF-kappaB activation. These findings may have implications for the treatment of acute and chronic pancreatitis and pancreatic cancer.
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PMID:Antioxidants inhibit cytokine production and suppress NF-kappaB activation in CAPAN-1 and CAPAN-2 cell lines. 1176 72

A total of 309 Helicobacter pylori isolates from 18 different countries were analyzed with a previously developed lectin typing system. The system was developed by using a proteolytic pretreatment to enhance the carbohydrate fraction of the sample. Four lectins from Ulex europaeus, Lotus tetragonolobus, Erythrina cristigali, and Triticum vulgaris were used to type the strains. The lectins were chosen for their specificities for sugars commonly encountered in the lipopolysaccharide of H. pylori. The isolates were received from their parent institutions as pellets of biomass and were typed at one of three centers (in Ireland, Sweden, and Estonia). All 16 possible lectin reaction patterns were observed in the study, with the isolates with the predominant pattern exhibiting reactions with all the lectins in the panel. For European patients suffering from gastritis, an association was noted between lectin reaction pattern MH4 and atrophic chronic gastritis; isolates with lectin reaction pattern MH4 were isolated from patients with atrophic chronic gastritis, whereas isolates with this pattern were not isolated from patients with chronic gastritis (P = 0.0006). In addition, statistically significant relationships were noted between the lectin reaction pattern and the associated pathology of isolates from the Swedish population. Isolates with patterns MH13 and MH16, which had low lectin reactivities, correlated with nonulcer disease (P = 0.0025 and P = 0.0002, respectively), and all four isolates from adenocarcinoma patients were characterized as possessing reaction pattern MH16. In contrast, isolates with lectin reaction patterns MH1 and MH10, which had high lectin reactivities, were associated with ulcer disease (P = 0.046 and P = 0.0022, respectively).
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PMID:Phenotypic variation of Helicobacter pylori isolates from geographically distinct regions detected by lectin typing. 1177 20

Zerumbone (ZER), a sesquiterpene from the edible plant Zingiber zerumbet Smith, has recently been found to suppress tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus activation in a potent manner. In the present study, we evaluated the anti-inflammatory and chemopreventive potentials of ZER in a variety of cell culture experiments. ZER effectively suppressed TPA-induced superoxide anion generation from both NADPH oxidase in dimethylsulfoxide-differentiated HL-60 human acute promyelocytic leukemia cells and xanthine oxidase in AS52 Chinese hamster ovary cells. The combined lipopolysaccharide- and interferon-gamma-stimulated protein expressions of inducible nitric oxide synthase and cyclooxygenase (COX)-2, together with the release of tumor necrosis factor-alpha, in RAW 264.7 mouse macrophages were also markedly diminished. These suppressive events were accompanied with a combined decrease in the medium concentrations of nitrite and prostaglandin E(2), while the expression level of COX-1 was unchanged. ZER inhibited the proliferation of human colonic adenocarcinoma cell lines (LS174T, LS180, COLO205, and COLO320DM) in a dose-dependent manner, while the growth of normal human dermal (2F0-C25) and colon (CCD-18 Co) fibroblasts was less affected. It also induced apoptosis in COLO205 cells, as detected by dysfunction of the mitochondria transmembrane, Annexin V-detected translocation of phosphatidylserine, and chromatin condensation. Intriguingly, alpha-humulene, a structural analog lacking only the carbonyl group in ZER, was virtually inactive in all experiments conducted, indicating that the alpha,beta-unsaturated carbonyl group in ZER may play some pivotal roles in interactions with unidentified target molecule(s). Taken together, our results indicate that ZER is a food phytochemical that has distinct potentials for use in anti-inflammation, chemoprevention, and chemotherapy strategies.
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PMID:Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the alpha,beta-unsaturated carbonyl group is a prerequisite. 1241 47

In vitro and in vivo studies from various groups have suggested that Helicobacter pylori lipopolysaccharide (LPS) Lewis x (Le(x)) antigens mediate bacterial adhesion. We have now reevaluated this hypothesis by studying the adherence in situ of H. pylori strain 11637 and its corresponding Le(x)-negative rfbM mutant to human gastric mucosa from patients (n = 22) with various gastric pathologies. Significant binding of the parent strain was observed in only 8 out of 22 sections; in four out of eight patients, the Le(x)-negative mutant bound less well. One of these four patients displayed no gastric abnormalities, and the other three showed dysplasia, metaplasia, and adenocarcinoma, respectively; hence, we are unable to define the circumstances under which LPS-mediated adhesion takes place. We conclude that H. pylori LPS plays a distinct but minor role in adhesion.
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PMID:Limited role of lipopolysaccharide Lewis antigens in adherence of Helicobacter pylori to the human gastric epithelium. 1270 61

The liver is generally considered negative for the vitamin D nuclear receptor (VDR(n)), even though several studies have shown significant effects of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on liver cell physiology. The low abundance of VDR(n) in the liver led us to propose that hepatocytes (the largest hepatic cell population) were most likely negative for the receptor, whereas the small hepatic sinusoidal and ductular cell populations that contain cell types known to express VDR(n) in other tissues should express the receptor. Using freshly isolated cells from normal livers as well as biliary and epithelial hepatic cell lines, our data show that the human, rat, and mouse hepatocytes express very low VDR(n) messenger RNA (mRNA) and protein levels. In contrast, sinusoidal endothelial, Kupffer, and stellate cells of normal rat livers as well as the mouse biliary cell line BDC and rat hepatic neonatal epithelial SD6 cells clearly expressed both VDR(n) mRNA and protein. In addition, specimens of human hepatocarcinoma as well as intrahepatic colon adenocarcinoma metastases were also found to express the VDR(n) gene transcript. Kupffer, stellate, and endothelial cells responded to 1,25(OH)(2)D(3) by a significant increase in the CYP24, indicating that the VDR(n) is fully functional in these cells. In conclusion, selective hepatic cell populations are targets for the vitamin D endocrine/paracrine/intracrine system.
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PMID:The normal liver harbors the vitamin D nuclear receptor in nonparenchymal and biliary epithelial cells. 1271 84

Infection with Helicobacter pylori, a Gram-negative, microaerophilic, flagellated bacteria that adheres to human gastric mucosa, is strongly associated with gastric ulcers and adenocarcinoma. The mechanisms through which gastric epithelial cells recognize this organism are unclear. In this study we evaluated the interactions between the Toll-like receptors (TLRs) and H. pylori-mediated NF-kappa B activation and the induction of chemokine mRNA expression. By reverse transcriptase-PCR we determined that MKN45 gastric epithelial cells express low but detectable amounts of TLR2, -4, and -5 but no MD-2. To determine which, if any, TLRs may play a role in the response of epithelial cells to H. pylori, HEK293 cells were cotransfected with the NF-kappa B-Luc reporter, CD14 and MD2 expression plasmids, and expression plasmids for TLR2, TLR4, or TLR5. Infection of the cultures with H. pylori (strain 26695) induced NF-kappa B activity in cells transfected with TLR2 and TLR5, but not TLR4. Consistent with the HEK293 experiments, H. pylori-induced NF-kappa B activation was decreased in MKN45 gastric epithelial cells by transfection of dominant-negative versions of TLR2 and TLR5 but not TLR4. Highly purified lipopolysaccharide from H. pylori strain 26695 activated NF-kappa B in HEK293 via TLR2 but not TLR4. Partially purified flagellin from H. pylori was also capable of inducing NF-kappa B activation in HEK cells transfected with TLR5. Additionally, chemokine gene expression was induced by H. pylori in HEK293 cells following stable transfection with TLR2 or TLR5 expression plasmids. These studies demonstrate that gastric epithelial cells recognize and respond to H. pylori infection at least in part via TLR2 and TLR5. Furthermore, the unique lipopolysaccharide of H. pylori is a TLR2, not a TLR4 agonist.
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PMID:Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells. 1280 70

Mammalian target of rapamycin (mTOR) and phosphatidylinositol 3-kinase (PI3K) regulate cell growth, protein synthesis, and apoptosis in response to nutrients and mitogens. As an important source of nitric oxide during inflammation, human inducible nitric oxide synthase also plays a role in the regulation of cytokine-driven cell proliferation and apoptosis. The role of mTOR and PI3K in the activation of human inducible nitric oxide synthase transcription by cytokines and lipopolysaccharide (LPS) was investigated in lung epithelial adenocarcinoma (A549) cells. LY294002, a dual mTOR and PI3K inhibitor, blocked human inducible nitric oxide synthase (hiNOS) promoter activation and mRNA induction by cytokines and LPS in a PI3K-independent fashion. On gene expression analysis, LY294002 selectively blocked the induction of a subset of 14 LPS/interferon-gamma (IFN-gamma)-induced genes, previously characterized as signal transducer and activator of transcription-1 (STAT1)-dependent. LY294002, but not wortmannin, inhibited LPS/IFN-gamma-dependent STAT1 phosphorylation at Ser-727 and STAT1 activity. Consistent with dual inhibition of mTOR and PI3K by LY294002, dominant-negative mTOR, anti-mTOR small interfering RNA, or rapamycin each inhibited phosphorylation of STAT1 only in the presence of wortmannin. LPS/IFN-gamma led to the formation of a macromolecular complex containing mTOR, STAT1, as well as protein kinase C delta, a known STAT1alpha kinase. Thus, LPS and IFN-gamma activate the PI3K and mTOR pathways, which converge to regulate STAT1-dependent transcription of pro-apoptotic and pro-inflammatory genes in a rapamycin-insensitive manner.
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PMID:Stimulation of signal transducer and activator of transcription-1 (STAT1)-dependent gene transcription by lipopolysaccharide and interferon-gamma is regulated by mammalian target of rapamycin. 1280 16


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