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)

We used an experimental murine cancer metastasis model in which a colon adenocarcinoma cell line generates lung metastases, whose growth is stimulated in response to injection of bacterial lipopolysaccharide (LPS), to investigate the role of NF-kappaB in inflammation-induced tumor growth. We found that LPS-induced metastatic growth response in this model depends on both TNFalpha production by host hematopoietic cells and NF-kappaB activation in tumor cells. Inhibition of NF-kappaB in both colon and mammary carcinoma cells converts the LPS-induced growth response to LPS-induced tumor regression. The latter response is TNFalpha-independent, but depends on another member of the TNF superfamily, TRAIL, whose receptor is induced in NF-kappaB-deficient cancer cells.
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PMID:Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression. 1538 May 20

Infection with Helicobacter pylori, a Gram-negative bacterium, is strongly associated with gastric ulcers and adenocarcinoma. The mechanisms by which the innate immune system recognizes H. pylori lipopolysaccharide (LPS) remain unclear. Contradictory reports exist that suggest that Toll-like receptors are involved. In this study we evaluated the interactions of Toll-like receptors with LPS from different strains of H. pylori. Using reporter cell lines, as well as HEK293 cells transfected with either CD14 and TLR4, or CD14 and TLR2, we show that H. pylori LPS-induced cell activation is mediated through TLR2. In addition, for the first time, we report that LPS from some H. pylori strains are able to antagonize TLR4. The antagonistic activity of H. pylori LPS from certain strains, as well as the activation via TLR2, might give H. pylori an advantage over the host that may be associated with the clinical outcome of H. pylori infection.
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PMID:Lipopolysaccharides from Helicobacter pylori can act as antagonists for Toll-like receptor 4. 1576 Apr 52

Helicobacter pylori (H. pylori) colonizes the gastric mucosa of a half of the mankind. Duodenal ulcer is found in 15-25%, gastric ulcer in 13%, while gastric adenocarcinoma develops in 1% of all infected individuals. Pathogenesis of H. pylori infection is related to the virulence factors of the bacterium, environmental (dietary habits, hygiene, stress) and host factors (age, sex, blood type). Colonization of the gastric mucosa is related to the motility of the bacterium, presence of lipopolysaccharide (LPS) and various bacterial enzymes. Gastric mucosal injury is the result of H. pylori LPS, vacuolization cytotoxin (vacA), cytotoxin associated protein (cagA), heat shock proteins and factors responsible for neutrophil chemotaxis and activity. H. pylori colonizes the gastric mucosa and zones of ectopic gastric epithelium. H. pylori infection is transmitted via oral-oral, fecal-oral and iatrogenic way (during endoscopy). Higher prevalence of the infection is associated with lower socioeconomic level, lack of drinking water, and living in a community. Acute H. pylori gastritis is superficial pangastritis progressing into the chronic phase after 7-10 days. Gastric mucosal atrophy and intestinal metaplasia can develop during the course of H. pylori infection. Clearly defined factors that influence the outcome of H. pylori infection include bacterial strain, distribution of gastritis, acid secretion and gastric mucosal atrophy.
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PMID:[Pathogenesis of Helicobacter pylori infection--bacterium and host relationship]. 1579 58

Helicobacter pylori (H. pylori), a long term colonizer of human stomach is known to infect a half of mankind. Gastric and duodenal ulcer, gastric adenocarcinoma and MALT lymphoma develop in a subset of infected individuals. Pathogenesis of H. pylori infection is based on the long-term host to bacterial interaction and affected by the virulence factors of the bacterium, environmental and host factors (age, sex, blood type). Mucosal inflammation is the basic principle mechanism underlying the disease development in which tissue destruction may be initiated and maintained by both the bacterial toxins (CagA, VacA, LPS) and immune responses by the host. Immune evasion with bacterial modulation of host response affects the long-term host colonization. Colonization is also affected by urease and/or motility of the bacterium, presence of lipopolysaccharide (LPS) and various bacterial enzymes. Gastric mucosal atrophy and intestinal metaplasia can develop during the course of H. pylori infection predisposing to carcinogenesis. Host cytokine gene polymorphism would be the one explanation for host susceptibility to peptic ulcer or gastric cancer. Investigation into the pathogenesis of H. pylori related diseases could provide an answer to the impact of chronic host to microbial interaction resulting human diseases.
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PMID:[Pathogenesis of Helicobacter pylori infection]. 1617 34

Helicobacter pylori causes gastritis and some infections result in peptic ulceration, gastric adenocarcinoma or gastric lymphoma. A critical step in the pathogenesis of these diseases is the ability of H. pylori to adhere to gastric epithelial cells. A role for the lipopolysaccharide O-antigen side-chain in this process has previously been identified. In this study, evidence is presented that the receptor recognized by the O-antigen side-chain is galectin-3, a beta-galactoside-binding lectin. A variety of functions have been ascribed to galectin-3 including modulation of extracellular adhesion and chemotaxis of monocytes and neutrophils. Expression of galectin-3 is upregulated by gastric epithelial cells following adhesion of H. pylori, suggesting that in addition to colonization this protein also plays a role in the host response to infection. Upregulation of galectin-3 is inhibited by treating gastric epithelial cells with the mitogen-activated protein kinase (MAPK) inhibitors U0126 or PD098059 and does not occur in cells infected with either H. pylori cagE or cagA isogenic mutants. This implies that H. pylori-mediated expression of galectin-3 is dependent on delivery of CagA into the host cell cytosol and the subsequent stimulation of MAPK signalling. A further consequence of H. pylori adhesion is that it elicits a rapid release of galectin-3 from infected cells. A role for this phenomenon in initiating the trafficking of phagocytic cells to the site of infection is discussed.
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PMID:Galectin-3 binds to Helicobacter pylori O-antigen: it is upregulated and rapidly secreted by gastric epithelial cells in response to H. pylori adhesion. 1636 65

The synthesis of nitric oxide by inducible nitric-oxide synthase (iNOS) plays an important role in the innate immune response by promoting microbial killing and cell damage. In response to inflammatory cytokines and bacterial products, the human iNOS (hiNOS) gene undergoes rapid transcriptional activation via binding of stimulatory transcription factors (e.g. AP-1 and NF-kappaB) to its 5'-flanking region. However, maximal hiNOS promoter induction was suppressed via an unknown phosphatidylinositol 3-kinase (PI3K)-dependent mechanism. We hypothesized that inhibition of the transcription factor FKHRL1 by the PI3K/protein kinase B pathway attenuates hiNOS promoter induction by bacterial lipopolysaccharide and interferon-gamma (LPS/IFN-gamma). Human lung epithelial adenocarcinoma (A549) cells were transiently transfected with an 8.3-kb hiNOS promoter luciferase reporter construct. Co-expression of dominant-negative protein kinase B potentiated LPS/IFN-gamma-stimulated hiNOS promoter activity. In response to LPS/IFN-gamma, FKHRL1 was phosphorylated in a PI3K- and time-dependent fashion. Co-expression of constitutively active FKHRL1 increased hiNOS promoter activity and mRNA levels. Dominant-negative siRNA expression showed that FKHRL1 was necessary for the inhibitory effects of PI3K on hiNOS induction. The same effect was observed upon mutation of a consensus FKHRL1-binding site in the hiNOS promoter. By gel-shift analysis, the corresponding oligonucleotide probe bound endogenous FKHRL1 in an LPS/IFN-gamma- and PI3K-sensitive fashion. Regulation of the hiNOS promoter by FKHRL1 represents a potentially important molecular mechanism by which the PI3K pathway might suppress pro-inflammatory and proapoptotic responses to cytokines and bacterial products.
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PMID:Phosphatidylinositol 3-kinase-dependent suppression of the human inducible nitric-oxide synthase promoter is mediated by FKHRL1. 1668 94

Peptic ulcer disease (PUD) occurs after a long-term Helicobacter pylori infection. However, the disease can develop earlier, and rare cases have been observed in children, suggesting that these H. pylori strains may be more virulent. We used suppressive subtractive hybridization for comparative genomics between H. pylori strains isolated from a 5-year-old child with duodenal ulcer and from a sex- and age-matched child with gastritis only. The prevalence of the 30 tester-specific subtracted sequences was determined on a collection of H. pylori strains from children (15 ulcers and 30 gastritis) and from adults (46 ulcers and 44 gastritis). Two of these sequences, jhp0562 (80.0% versus 33.3%, P = 0.008) and jhp0870 (80.0% versus 36.7%, P = 0.015), were highly associated with PUD in children and a third sequence, jhp0828, was less associated (40.0% versus 10.0%, P = 0.048). Among adult strains, none of the 30 sequences was associated with PUD. However, both jhp0562 and jhp0870 were less prevalent in adenocarcinoma strains than in PUD strains from children and adults, the difference being statistically significant for jhp0870. In conclusion, two H. pylori genes were identified as being strongly associated with PUD in children, and their putative roles as an outer membrane protein for jhp0870 and in lipopolysaccharide biosynthesis for jhp0562, suggest that they may be novel virulence factors of H. pylori.
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PMID:Identification of markers for Helicobacter pylori strains isolated from children with peptic ulcer disease by suppressive subtractive hybridization. 1679 Jul 80

The hedgehog (Hh) signaling pathway, which functions as an organizer in embryonic development, is implicated in the development of various tumors. In pancreatic cancer, pathway activation is reported to result from aberrant expression of the ligand, sonic Hh (Shh). However, the details of the mechanisms regulating Shh expression are not yet known. We hypothesized that nuclear factor-kappaB (NF-kappaB), a hallmark transcription factor in inflammatory responses, contributes to the overexpression of Shh in pancreatic cancer. In the present study, we found a close positive correlation between NF-kappaB p65 and Shh expression in surgically resected pancreas specimens, including specimens of chronic pancreatitis and pancreatic adenocarcinoma. We showed that blockade of NF-kappaB suppressed constitutive expression of Shh mRNA in pancreatic cancer cells. Further activation of NF-kappaB by inflammatory stimuli, including interleukin-1beta, tumor necrosis factor-alpha, and lipopolysaccharide, induced overexpression of Shh, resulting in activation of the Hh pathway. Overexpression of Shh induced by these stimuli was also suppressed by blockade of NF-kappaB. NF-kappaB-induced Shh expression actually activated the Hh pathway in a ligand-dependent manner and enhanced cell proliferation in pancreatic cancer cells. In addition, inhibition of the Hh pathway as well as NF-kappaB suppressed the enhanced cell proliferation. Our data suggest that NF-kappaB activation is one of the mechanisms underlying Shh overexpression in pancreatic cancer and that proliferation of pancreatic cancer cells is accelerated by NF-kappaB activation in part through Shh overexpression.
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PMID:Nuclear factor-kappaB contributes to hedgehog signaling pathway activation through sonic hedgehog induction in pancreatic cancer. 1684 49

Heparin is an excellent inhibitor of P- and L-selectin binding to the carbohydrate determinant, sialyl Lewis(x). As a consequence of its anti-selectin activity, heparin attenuates metastasis and inflammation. Here we show that fucosylated chondroitin sulfate (FucCS), a polysaccharide isolated from sea cucumber composed of a chondroitin sulfate backbone substituted at the 3-position of the beta-D-glucuronic acid residues with 2,4-disulfated alpha-L-fucopyranosyl branches, is a potent inhibitor of P- and L-selectin binding to immobilized sialyl Lewis(x) and LS180 carcinoma cell attachment to immobilized P- and L-selectins. Inhibition occurs in a concentration-dependent manner. Furthermore, FucCS was 4-8-fold more potent than heparin in the inhibition of the P- and L-selectin-sialyl Lewis(x) interactions. No inhibition of E-selectin was observed. FucCS also inhibited lung colonization by adenocarcinoma MC-38 cells in an experimental metastasis model in mice, as well as neutrophil recruitment in two models of inflammation (thioglycollate-induced peritonitis and lipopolysaccharide-induced lung inflammation). Inhibition occurred at a dose that produces no significant change in plasma activated partial thromboplastin time. Removal of the sulfated fucose branches on the FucCS abolished the inhibitory effect in vitro and in vivo. Overall, the results suggest that invertebrate FucCS may be a potential alternative to heparin for blocking metastasis and inflammatory reactions without the undesirable side effects of anticoagulant heparin.
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PMID:Selectin blocking activity of a fucosylated chondroitin sulfate glycosaminoglycan from sea cucumber. Effect on tumor metastasis and neutrophil recruitment. 1737 80

An LD-heptosyltransferase gene, HP1191 (waaF), involved in biosynthesis of the inner-core region of Helicobacter pylori strain 26695 lipopolysaccharide (LPS), has been cloned and its function established by complementation of Salmonella enterica serovar Typhimurium waaF mutant strain, strain 3789. Insertional inactivation of the HP1191 open reading frame in strain 26695 resulted in the formation of a deeply truncated LPS molecule, as observed using SDS-PAGE. Subsequent compositional and fatty acid analyses, followed by capillary electrophoresis - mass spectrometry and nuclear magnetic resonance studies established its structure as the following: PE-->7)-L-alpha-D-Hepp-(1-->5)-alpha-Kdop-(2-->6)-Lipid A, where PE represents a phosphoethanolamine group, LD-Hep represents L-glycero-D-manno-heptose, and Kdo represents 3-deoxy-D-manno-oct-2-ulosonic acid. This structural analysis identifies the activity of HP1191 as a heptosyltransferase and a waaF homolog. In vitro invasion assays using human cultured gastric adenocarcinoma cells as a host cell model confirmed that the level of invasion was unaffected for an H. pylori HP1191::Kan deep-rough mutant strain compared with the wild-type strain 26695 expressing the O-chain polysaccharide, providing evidence that LPS is not a critical factor for invasion.
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PMID:Characterization of a waaF mutant of Helicobacter pylori strain 26695 provides evidence that an extended lipopolysaccharide structure has a limited role in the invasion of gastric cancer cells. 1790


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