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)

The homing of lymphoid cells to mucosa-associated lymphoid tissue is, amongst other factors, influenced by the nature of the antigen used to induce an immune response. To study this phenomenon we have monocolonized rats with a type 1 fimbriated Escherichia coli O6K13H1 strain and compared the secretory antibody response to colonization with the primary and secondary response obtained in rats immunized in the Peyer's patches (PP). Samples were tested with respect to the titres of antibodies against two antigens present on the E. coli strain: O6 lipopolysaccharide (LPS) and type 1 fimbrial antigen. In the primary immunized animals, IgA anti-fimbrial antibodies were mainly seen in milk and IgA anti-LPS antibodies mostly found in bile. In the booster immunized, and in the monocolonized, animals there was a shift of the antibody response towards the bile. Thus anti-fimbrial antibodies appeared in milk at approximately the same or at a lower level than in bile and the IgA anti-LPS antibodies were almost completely absent in the milk. The IgG antibody response of the animals immunized in the PP was primarily confined to milk for both anti-LPS and anti-fimbrial antibodies, while the colonized animals responded with higher levels in bile than in milk. IgM antibodies were only seen in the milk, except in primary immunized animals in which biliary IgM antibodies also were found. The data illustrate that: (i) primary stimulated cells predestined to produce IgA anti-LPS antibodies home mainly to the intestine, while cells predestined to anti-fimbrial antibody production have a greater tendency to populate the mammary gland; (ii) after repeated antigen stimulation and maturation of the immune response the cells are directed from the mammary gland to the intestine. We thus conclude that the nature of the antigen and the stage of lymphocyte maturation influences the homing of the cells and the appearance of various antibodies in different secretions.
 ...
PMID:The secretory antibody response in milk and bile against fimbriae and LPS in rats monocolonized or immunized in the Peyer's patches with Escherichia coli. 197 93

The mucosa-associated lymphoid tissue may deviate from its systemic counterpart in being able to discriminate between microbial and nonmicrobial antigens. To study this, the systemic and mucosal antibody responses to bacterial and food antigens were followed in parallel in female rats during two pregnancies and lactation periods. Germfree rats were monocolonized with an Escherichia coli O6K13H1 strain, and their diet was switched to pellets containing large amounts of ovalbumin and beta-lactoglobulin. Antibodies against O6 lipopolysaccharide already appeared in serum and bile 1 week after colonization, and those against type 1 fimbriae appeared a few weeks later. Serum immunoglobulin G antibodies against the E. coli enzyme beta-galactosidase were found in moderate titers in all rats after 16 weeks of exposure. In contrast, few rats had detectable antibody levels against the dietary proteins ovalbumin and beta-lactoglobulin in serum or bile even after 16 weeks of exposure. In the milk, antibodies against E. coli beta-galactosidase and type 1 fimbriae reached the highest titers, while moderate titers were found against the food antigens and against O6 lipopolysaccharide. The difference in immune reactivity against bacterial versus dietary antigens was not likely due to insufficient amounts of the latter reaching lymphoid tissue, since (i) uptake studies indicated that ovalbumin was more efficiently taken up than endotoxin and (ii) the same difference in antigenicity between ovalbumin and E. coli was seen after immunization directly into Peyer's patches. We therefore suggest that a prerequisite for a strong mucosal antibody response is that the antigen be encountered by the gut-associated lymphoid tissue within microorganisms capable of stimulating antigen presentation.
 ...
PMID:Difference between bacterial and food antigens in mucosal immunogenicity. 266 82

About half of the world's population carries Helicobacter pylori, a gram-negative, spiral bacterium that colonizes the human stomach. The link between H. pylori and, ulceration as well as its association with the development of both gastric cancer and mucosa-associated lymphoid tissue lymphoma in humans is a serious public health concern. The publication of the genome sequences of two stains of H. pylori gives rise to direct evidence on the genetic diversity reported previously with respect to gene organization and nucleotide variability from strain to strain. The genome size of H. pylori strain 26695 is 1,6697,867 bp and is 1,643,831 bp for strain J99. Approximately 89% of the predicted open reading frames are common to both of the strains, confirming H. pylori as a single species. A region containing approximately 45% of H. pylori strain-specific open reading frames, termed the plasticity zone, is present on the chromosomes, verifying that some strain variability exists. Frequent alteration of nucleotides in the third position of the triplet codons and various copies of insertion elements on the individual chromosomes appear to contribute to distinct polymorphic fingerprints among strains analyzed by restriction fragment length polymorphisms, random amplified polymorphic DNA method, and repetitive element-polymerase chain reaction. Disordered chromosomal locations of some genes seen by pulsed-field gel electrophoresis are likely caused by rearrangement or inversion of certain segments in the genomes. Cloning and functional characterization of the genes involved in acidic survival, vacuolating toxin, cag-pathogenicity island, motility, attachment to epithelial cells, natural transformation, and the biosynthesis of lipopolysaccharides have considerably increased our understanding of the molecular genetic basis for the pathogenesis of H. pylori. The homopolymeric nucleotide tracts and dinucleotide repeats, which potentially regulate the on- and off-status of the target genes by the strand-slipped mispairing mechanism, are often found in the genes encoding the outer-membrane proteins, in enzymes for lipopolysaccharide synthesis, and within DNA modification/restriction systems. Therefore, these genes may be involved in the H. pylori-host interaction.
 ...
PMID:Contributions of genome sequencing to understanding the biology of Helicobacter pylori. 1054 95

Helicobacter pylori (HP), undoubtedly, the most common world-wide infection plays an important role in pathogenesis of peptic ulcer. Proof for a causal role for HP in peptic ulcer rests in two major points; 1) the majority of ulcer patients are HP infected and the prevalence of this infection for both gastric ulcer (GU) and duodenal ulcer (DU) is much higher than for gender- and age-adjusted controls and 2) the cure of HP infection dramatically reduces ulcer recurrence. Conclusions regarding the mechanisms by which HP induces peptic ulcer are restricted mainly to studies observing the consequences of its eradication by antibiotics combined with gastric inhibitors or bismuth agents. Several specific virulence factors such as cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) as well as other noxious substances including ammonia, lipopolysaccharide (endotoxin), platelet activating factor (PAF), nitric oxide (NO) and others have been implicated in gastritis and were found to be significantly more frequent in gastric cancer than in gender- and age-matched controls, especially in younger generation. Chronic inflammation, atrophic gastritis, intestinal metaplasia, impaired defense mechanisms combined with hypergastrinemia, deficiency of vitamin C in the stomach , excessive oxygen metabolites and epithelial cell proliferation have been associated with gastric cancer. This multi-step pathway originally proposed by Correa and his colleagues, long before the HP was discovered in the stomach, leads to cancer but may be reversed by eradication of HP. This is, however, a controversial issue because gastric atrophy and intestinal metaplasia may be also caused by other factors such as bile reflux, dietary irritants, and autoimmunity. The implication of HP in MALT-lymphoma is based on the observations that eradication of HP in early stage of low-grade of this tumor leads to complete remission. The significance of HP in non-ulcer dyspepsia remains questionable and requires further studies.
 ...
PMID:Helicobacter pylori associated gastric pathology. 1069 52

Toll-like receptor 4, as part of innate immune response, is the main receptor for lipopolysaccharide on marginal zone B cells. The rare allele of TLR4 Asp299Gly attenuates receptor signaling and diminishes the inflammatory response. We genotyped 87 patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, 594 Helicobacter pylori positive controls and 358 healthy blood donors to investigate an association of TLR4 Asp299Gly in the development of gastric MALT lymphoma. Heterozygote genotype was significantly less frequent in patients with gastric MALT lymphoma compared to H. pylori-infected controls (4.6% vs. 11.6%, Fischer's exact P=0.019, odds ratio=0.37, 95% confidence interval 0.13-1.03). Because 10% of caucasians are carriers of the rare allele G TLR4 Asp299Gly appears to be only one factor in the genetic susceptibility to gastric lymphoma. Further studies in larger samples are needed to confirm our findings and fully elucidate the role of TLR4 and its genetic variants in the pathophysiology of H. pylori infection and gastric lymphoma.
 ...
PMID:Association study of a functional Toll-like receptor 4 polymorphism with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma. 1601 31

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.
 ...
PMID:[Pathogenesis of Helicobacter pylori infection]. 1617 34

The mucosal immune system plays a central role in both the transmission of HIV infection and the pathogenesis of AIDS. Most HIV infections are acquired through mucosal transmission, and quantitative and qualitative defects of mucosal immunity are consistently present in all stages of pathogenic HIV and SIV infections. A series of recent studies has emphasized the role of a rapid, dramatic, and largely irreversible depletion of mucosa-associated lymphoid tissue-based memory CD4(+)CCR5(+) T-cells as a key determinant of disease progression in HIV-infected individuals and SIV-infected macaques. It has also been proposed that, in order to be effective, an AIDS vaccine should prevent the early depletion of these mucosal CD4(+) T-cells. However, the observation of depletion of mucosal CD4(+) T-cells during the primary phase of nonpathogenic SIV infection of natural SIV hosts, such as sooty mangabeys and African green monkeys, suggests that additional pathogenic factors are involved in the AIDS-associated mucosal immune dysfunction. These factors may include: (i) selective depletion of specific CD4(+) T-cell subsets; (ii) dysfunction of other (non-CD4(+)) immune cells; and (iii) generalized immune activation. Importantly, the mucosal immune dysfunction observed during pathogenic HIV and SIV infection is associated with translocation of microbial products (i.e. lipopolysaccharide) from the intestinal lumen to the systemic circulation where they may be responsible, at least in part, for the chronic immune activation that follows pathogenic HIV and SIV infections. The role of mucosal immunity in AIDS pathogenesis emphasizes the importance of understanding whether and to what extent the HIV-associated depletion of mucosal CD4(+) T-cells is reversible after prolonged suppression of virus replication with antiretroviral therapy. Further studies of mucosal immunity during primate lentiviral infections will be needed to better understand, and ultimately prevent and treat, the mechanisms underlying the AIDS-associated mucosal immune dysfunction.
 ...
PMID:Mucosal immune dysfunction in AIDS pathogenesis. 1838 79

Human brucellosis is caused mainly by Brucella melitensis, which is often acquired by ingesting contaminated goat or sheep milk and cheese. Bacterial factors required for food-borne infection of humans by B. melitensis are poorly understood. In this study, a mouse model of oral infection was characterized to assess the roles of urease, the VirB type IV secretion system, and lipopolysaccharide for establishing infection through the digestive tract. B. melitensis strain 16M was consistently recovered from the mesenteric lymph node (MLN), spleen, and liver beginning at 3 or 7 day postinfection (dpi). In the gut, persistence of the inoculum was observed up to 21 dpi. No inflammatory lesions were observed in the ileum or colon during infection. Mutant strains lacking the ureABC genes of the ure1 operon, virB2, or pmm encoding phosphomannomutase were constructed and compared to the wild-type strain for infectivity through the digestive tract. Mutants lacking the virB2 and pmm genes were attenuated in the spleen (P < 0.05) and MLN (P < 0.001), respectively. The wild-type and mutant strains had similar levels of resistance to low pH and 5 or 10% bile, suggesting that the reduced colonization of mutants was not the result of reduced resistance to acid pH or bile salts. In an in vitro lymphoepithelial cell (M-cell) model, B. melitensis transited rapidly through polarized enterocyte monolayers containing M-like cells; however, transit through monolayers containing only enterocytes was reduced or absent. These results indicate that B. melitensis is able to spread systemically from the digestive tract after infection, most likely through M cells of the mucosa-associated lymphoid tissue.
 ...
PMID:Establishment of systemic Brucella melitensis infection through the digestive tract requires urease, the type IV secretion system, and lipopolysaccharide O antigen. 1965 62

BCL10 is an apoptotic regulatory molecule identified through its direct involvement in t(1; 14)(p22; q32) of mucosa-associated lymphoid tissue lymphoma, and was implicated in the pathogenesis of this and several other tumour types. BCL10 was recognized as an antigen receptor-specific regulator of NF-kappaB, which showed close association with immune responses. In this study, we cloned and characterized BCL10 from the porcine spleen and analysed its genomic structure. BCL10 was mapped to SSC4q21-q23 by the IMpRH panels, it is closely linked to the marker S0161 and SW1461. This gene has three exons and two introns. Reverse transcriptase-polymerase chain reaction analyses showed that BCL10 was widely expressed in all the examined tissues. Transient transfection indicated that porcine BCL10 was located in cytoplasm in Pig Kidney Epithelial cells. BCL10 gene displays the opposite expression trend between the two treatments mimic virus and bacteria of polyriboinosinic-polyribocytidylic acid (Poly I:C) and lipopolysaccharide (LPS). The level of the BCL10 mRNA was up-regulated during 12-24 h and peaking at 48 h when treated with LPS, whereas it was down-regulated during 0-48 h and highest at 0 h (cells without treating with Poly I:C) when treated with Poly I:C. One single nucleotide polymorphism (SNP) site was identified in the 3'-untranslated region of porcine BCL10. Association analysis revealed that this SNP was significantly associated with intermediate cell mass (eosinophile granulocyte, basophile granulocyte and histoleucocyte) percentage, absolute intermediate cell mass count and mean red blood cell volume of 0-day-old pigs, and red blood cell count of 17-day-old pigs (P < 0.05), and also had significant associations with red blood cell count and haemoglobin concentration of 32-day-old pigs (P < 0.01).
 ...
PMID:BCL10 as a new candidate gene for immune response in pigs: cloning, expression and association analysis. 2019 35

Helicobacter pylori, the human pathogen that affects about half of the world population and that is responsible for gastritis, gastric ulcer and adenocarcinoma and MALT lymphoma, owes much of the integrity of its outer membrane on lipopolysaccharides (LPSs). Together with their essential structural role, LPSs contribute to the bacterial adherence properties, as well as they are well characterized for the capability to modulate the immuno-response. In H. pylori the core oligosaccharide, one of the three main domains of LPSs, shows a peculiar structure in the branching organization of the repeating units, which displayed further variability when different strains have been compared. We present here the crystal structure of ADP-L-glycero-D-manno-heptose-6-epimerase (HP0859, rfaD), the last enzyme in the pathway that produces L-glycero-D-manno-heptose starting from sedoheptulose-7-phosphate, a crucial compound in the synthesis of the core oligosaccharide. In a recent study, a HP0859 knockout mutant has been characterized, demonstrating a severe loss of lipopolysaccharide structure and a significant reduction of adhesion levels in an infection model to AGS cells, if compared with the wild type strain, in good agreement with its enzymatic role. The crystal structure reveals that the enzyme is a homo-pentamer, and NAD is bound as a cofactor in a highly conserved pocket. The substrate-binding site of the enzyme is very similar to that of its orthologue in Escherichia coli, suggesting also a similar catalytic mechanism.
 ...
PMID:The crystal structure of ADP-L-glycero-D-manno-heptose-6-epimerase (HP0859) from Helicobacter pylori. 2197 83


1 2 Next >>