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)

The inflammatory lesions associated with Helicobacter pylori gastritis and duodenitis contain large numbers of mononuclear cells. The close proximity of H. pylori to gastric mucosa suggests that the organism interacts with mononuclear cells, thereby modulating the inflammatory response. To investigate the role of monocytes/macrophages in this response, we examined the effect of whole H. pylori bacteria, H. pylori surface proteins, and H. pylori lipopolysaccharide (LPS) on purified human monocytes. Whole H. pylori and the extracted LPS induced expression of the monocyte surface antigen HLA-DR and interleukin-2 receptors, production of the inflammatory cytokines interleukin 1 and tumor necrosis factor (peptide and messenger RNA), and secretion of the reactive oxygen intermediate superoxide anion. Since H. pylori in vivo does not invade mucosal tissue, we determined whether soluble constituents of the bacteria could activate monocytes. Soluble H. pylori surface proteins, which are enriched for urease and do not contain LPS, stimulated phenotypic, transcriptional, and functional changes consistent with highly activated monocytes. These findings indicate that H. pylori is capable of activating human monocytes by an LPS-independent as well as an LPS-dependent mechanism. H. pylori activation of resident lamina propria macrophages and monocytes trafficking through the mucosa, leading to the secretion of increased amounts of inflammatory cytokines and reactive oxygen intermediates, could play an important role in mediating the inflammatory response associated with H. pylori gastritis and duodenitis.
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PMID:Soluble surface proteins from Helicobacter pylori activate monocytes/macrophages by lipopolysaccharide-independent mechanism. 184 39

Active Helicobacter pylori-associated gastritis is characterized by a dense mucosal infiltration with granulocytes. Since H. pylori is noninvasive, secondary signals must induce the accumulation of granulocytes. Interleukin-8 (IL-8) has been shown to play a key role in this event. Using competitive reverse transcriptase-PCR on mRNA from gastric biopsies, we could show a clear correlation between the amount of IL-8 transcripts and the activity of H. pylori gastritis. Due to the inability of the bacterium to invade host cells, the epithelial layer is a potential candidate as an IL-8 source. To study the mechanism of IL-8 induction, established gastric carcinoma epithelial cell lines (AGS and Kato III) and well-defined H. pylori strains were used in a modified in vitro system. The experimental design enabled us to prevent direct contact of bacteria with epithelial cells by use of a filter membrane which did not block secreted bacterial products crossing the membrane. The data clearly showed that the direct contact of the bacterial cell with the epithelial cell is necessary for optimal IL-8 production because not only live bacteria, but also metabolically inactive bacteria, increased IL-8 secretion. Neither purified lipopolysaccharide nor water-soluble protein fractions of H. pylori NCTC 11637 and Tx30a nor the cytotoxin of H. pylori was able to increase IL-8 production significantly by the epithelial cells used. Furthermore, preparations of total membrane and outer membrane proteins of H. pylori were not able to stimulate IL-8 release in vitro. Accumulatively, these results imply that active metabolism is not necessary for stimulation as long as there is an intact membrane aiding the presentation of a stimulating membrane complex or aggregate on the surface of the bacteria. From these results, we conclude that whole bacteria and their direct contact with epithelial cells may be critical for IL-8 induction in vivo.
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PMID:Role of adherence in interleukin-8 induction in Helicobacter pylori-associated gastritis. 928 28

Helicobacter pylori gastritis is characterized by leukocyte infiltration of the gastric mucosa. The aims of this study were to determine whether H. pylori-derived factors stimulate chemokine release from human monocytes and to ascertain whether H. pylori lipopolysaccharide (LPS) may be responsible for this effect. Human peripheral blood monocytes were exposed to an H. pylori water extract (HPE) or to purified H. pylori LPS. Levels of the chemokines interleukin-8 (IL-8), epithelial neutrophil-activating peptide 78 (ENA-78), and monocyte chemotactic protein 1 (MCP-1) were measured by enzyme-linked immunosorbent assay. The contribution of H. pylori LPS to monocyte activation was determined by using the LPS antagonist Rhodobacter sphaeroides lipid A (RSLA) and a blocking monoclonal antibody to CD14 (60bca). HPE increased monocyte secretion of IL-8, ENA-78, and MCP-1. Heat treatment of HPE did not reduce its ability to activate monocytes. Purified H. pylori LPS also stimulated monocyte chemokine production but was 1,000-fold less potent than Salmonella minnesota lipid A. RSLA blocked H. pylori LPS-induced monocyte IL-8 release in a dose-dependent fashion (maximal inhibition 82%, P < 0.001). RSLA also inhibited HPE-induced IL-8 release (by 93%, P < 0.001). The anti-CD14 monoclonal antibody 60bca substantially inhibited IL-8 release from HPE-stimulated monocytes (by 88%, P < 0.01), whereas the nonblocking anti-CD14 monoclonal antibody did not. These experiments with potent and specific LPS inhibitors indicate that the main monocyte-stimulating factor in HPE is LPS. H. pylori LPS, acting through CD14, stimulates human monocytes to release the neutrophil-activating chemokines IL-8 and ENA-78 and the monocyte-activating chemokine MCP-1. Despite its low relative potency, H. pylori LPS may play an important role in the pathogenesis of H. pylori gastritis.
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PMID:Helicobacter pylori lipopolysaccharide binds to CD14 and stimulates release of interleukin-8, epithelial neutrophil-activating peptide 78, and monocyte chemotactic protein 1 by human monocytes. 978 44

The protein C (PC) pathway has recently been suggested to play a role in the regulation of the inflammatory response. To further extend the anti-inflammatory effect of activated PC (APC) in vivo, particularly its biological relevance to human disease, the activity of APC in the mucosa of patients with Helicobacter pylori-associated gastritis and the effect of vacuolating cytotoxin (VacA), cytotoxin-associated antigen (CagA), and H. pylori lipopolysaccharide (LPS) on PC activation were evaluated. This study comprised 35 patients with chronic gastritis. There were 20 patients with and 15 without H. pylori infection. The levels of PC and APC-PC inhibitor (PCI) complex were measured by immunoassays. The level of PC was significantly decreased and the level of APC-PCI complex was significantly increased in biopsy specimens from gastric corpus and antrum in patients with H. pylori-associated gastritis as compared to H. pylori-negative subjects. The concentrations of VacA, CagA, and LPS were significantly correlated with those of the APC-PCI complex in biopsy mucosal specimens from the gastric corpus and antrum. H. pylori LPS, VacA, and CagA induced a dose-dependent activation of PC on the surface of monocytic cells. APC inhibited the secretion of tumor necrosis factor alpha (TNF-alpha) induced by H. pylori LPS. Overall, these results suggest that H. pylori infection is associated with increased APC generation in the gastric mucosa. The inhibitory activity of APC on TNF-alpha secretion may serve to protect H. pylori-induced gastric mucosal damage.
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PMID:Role of activated protein C in Helicobacter pylori-associated gastritis. 1076 83

In Helicobacter pylori gastritis, neutrophil activation and migration, which play central roles in the pathogenesis of the disease, are regulated by the neutrophil attractant chemokines interleukin 8 (IL-8) and Groalpha, whose secretion is induced by H. pylori. However, the modulation of the corresponding chemokine receptors CXCR1 and CXCR2 on human neutrophils under the influence of H. pylori has not been investigated. Incubation of neutrophils with cag(+) and cag deletion H. pylori strains resulted in a complete downregulation of the CXCR1 and the CXCR2 receptors after 0.5 h, as tested by fluorescence-activated cell sorter analysis, independent of the cag status. Downregulation of CXCR1 and CXCR2 seems to occur via receptor internalization and rapid degradation, as shown by confocal microscopy and immunoblotting. Neither the proinflammatory cytokines IL-8 and tumor necrosis factor alpha produced by the neutrophils themselves nor H. pylori lipopolysaccharide, which are the known regulators of these two chemokine receptors, was responsible for the downregulation. Reverse transcription-PCR analysis showed that CXCR1 and CXCR2 mRNAs of neutrophils were reduced at a later time than the CXCR1 and CXCR2 proteins. Moreover, cag(+) H. pylori strains induced significantly stronger downregulation of CXCR1 and CXCR2 mRNAs than the cag deletion mutant. Therefore, receptor protein and mRNA downregulation seem to be mediated by two independent mechanisms. Data obtained by immunohistochemistry suggested that downmodulation of CXCR1 and CXCR2 on neutrophils may also occur in vivo in the human stomach during H. pylori infection. Downregulation of CXCR1 and CXCR2 expression on neutrophils in H. pylori infection by H. pylori itself may represent a new mechanism of modulating neutrophil migration and activation in the gastric mucosa.
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PMID:Downregulation of CXCR1 and CXCR2 expression on human neutrophils by Helicobacter pylori: a new pathomechanism in H. pylori infection? 1555 97