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)

Although the antimicrobial activity of lactoferrin has been well described, its mechanism of action has been poorly characterized. Recent work has indicated that in addition to binding iron, human lactoferrin damages the outer membrane of gram-negative bacteria. In this study, we determined whether bovine lactoferrin and a pepsin-derived bovine lactoferrin peptide (lactoferricin) fragment have similar activities. We found that both 20 microM bovine lactoferrin and 20 microM lactoferricin release intrinsically labeled [3H]lipopolysaccharide ([3H]LPS) from three bacterial strains, Escherichia coli CL99 1-2, Salmonella typhimurium SL696, and Salmonella montevideo SL5222. Under most conditions, more LPS is released by the peptide fragment than by whole bovine lactoferrin. In the presence of either lactoferrin or lactoferricin there is increased killing of E. coli CL99 1-2 by lysozyme. Like human lactoferrin, bovine lactoferrin and lactoferricin have the ability to bind to free intrinsically labeled [3H]LPS molecules. In addition to these effects, whereas bovine lactoferrin was at most bacteriostatic, lactoferricin demonstrated consistent bactericidal activity against gram-negative bacteria. This bactericidal effect is modulated by the cations Ca2+, Mg2+, and Fe3+ but is independent of the osmolarity of the medium. Transmission electron microscopy of bacterial cells exposed to lactoferricin show the immediate development of electron-dense "membrane blisters." These experiments offer evidence that bovine lactoferrin and lactoferricin damage the outer membrane of gram-negative bacteria. Moreover, the peptide fragment lactoferricin has direct bactericidal activity. As lactoferrin is exposed to proteolytic factors in vivo which could cleave the lactoferricin fragment, the effects of this peptide are of both mechanistic and physiologic relevance.
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PMID:Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment. 842 97

Human milk is in several ways anti-inflammatory. This study investigates whether or not human milk lactoferrin (LF) in comparison with bovine LF can affect the IL-6 release from human cells. Human, as well as bovine, LF and a bactericidal pepsin-derived fragment of bovine LF (lactoferricin B) were found to suppress the IL-6 response in a monocytic cell line (THP-1) when stimulated by lipopolysaccharide (LPS). The suppression of bovine LF was similar to or higher than that of human LF. Lactoferricin B was the strongest inhibitor of the LPS-induced IL-6 response. A time-dependence regarding the inhibitory capacity of LF was found. For human LF, the strongest inhibition was observed when added 15-30 min after the addition of LPS. Addition of LF before the LPS induced an approximately 45% reduction of the IL-6 response. The results suggest an anti-inflammatory activity of both human and bovine LF, and of the LF fragment lactoferricin B through their suppressive effects on the cytokine release.
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PMID:Lactoferrin or a fragment thereof inhibits the endotoxin-induced interleukin-6 response in human monocytic cells. 882 74

The effects were examined of a pepsin hydrolysate of bovine lactoferrin on the proliferation of murine splenocytes. The hydrolysate enhanced [3H]thymidine uptake by splenocytes, but undigested bovine lactoferrin exerted an inhibitory effect. The hydrolysate had the ability to inhibit the blastogenesis that was induced by mitogens such as concanavalin A, phytohemagglutinin, and lipopolysaccharide; inhibition was similar to that with undigested lactoferrin. These results suggested that the hydrolysate contained both immunostimulatory and immunoinhibitory peptides. The stimulatory effect of the hydrolysate in the absence of mitogens was then explored in more detail using nonadherent splenocytes. The proliferative response of splenocytes to the hydrolysate was much greater in the fraction that was enriched with B cells than in the fraction that was enriched with T cells. The hydrolysate did not affect thymocyte proliferation. These data indicated that the adherent cells resembling macrophages and found among the splenocytes were not the target cells of the hydrolysate. The stimulatory effect of the hydrolysate was due to the activation of B cells by the hydrolysate and enhanced immunoglobulin production by splenocytes. Because the hydrolysate also enhanced the proliferation and immunoglobulin A production of Peyer's Patch cells, the immunostimulatory effect of the hydrolysate in vivo was examined using mice that had been orally immunized with cholera toxin. The concentrations of immunoglobulin A conjugated against cholera toxin in bile and in the intestinal contents of mice fed liquid diets containing 1% (wt/vol) lactoferrin hydrolysate were greater than those of mice fed control diets. This result suggested that the use of the lactoferrin hydrolysate is beneficial to enhance mucosal immunity.
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PMID:Immunomodulatory effect of bovine lactoferrin pepsin hydrolysate on murine splenocytes and Peyer's patch cells. 936 Dec 5

Anti-Yersinia ruckeri egg yolk immunoglobulin (IgY) was transferred to egg yolk after immunization of White Leghorn hens with formalin-killed whole cells of serovar 1 (RS1154) and serovar 2 (RS1153)Y. ruckeri and its lipopolysaccharide (LPS). The IgY was specific for its homologous LPS in western immunoblot, whereas some protein bands were commonly recognized, even by IgY from eggs of unimmunized hens. Purified LPS from both Y. ruckeri serovar types 1 and 2 had a very poor immunogenicity. The IgY activity was stable when processed into pellet form by a microbial transglutaminase treatment and showed a considerable resistance against acid pepsin for at least 2 h. Feeding specific anti-serovar 1 Y. ruckeri IgY to fish either before or after immersion infection produced marginal reductions in mortalities and in intestine infection. The same IgY did passively protect rainbow trout against infection when administered by intraperitoneal injection 4 h before an immersion challenge.
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PMID:Effects of hen egg yolk immunoglobulin in passive protection of rainbow trout against Yersinia ruckeri. 1063 61

BD5088 alpha-amylase derived from archaeal sources has characteristics of pH and temperature tolerance that are well suited to hydrolysis of starch in food processing applications. The production microorganism recipient strain, Pseudomonas fluorescens biovar I, strain MB101, was avirulent after oral administration to mice and does not represent an infectious threat to humans. Repeated dose gavage studies with BD5088 enzyme preparation, up to 13 weeks in duration, showed no systemic toxicity due to the oral route with an NOAEL of 890 mg/kg/day as Total Organic Solids. Some irritation occurred in the respiratory tract, which was considered to be a consequence of reflux and aspiration of test material that contained lipopolysaccharide from the Pseudomonas production strain. A 2-week dietary study (0 and 310 mg/kg/day) confirmed that there were no respiratory tract effects related to oral ingestion. There was no genotoxic activity based on Ames, mouse lymphoma, mouse micronucleus, and rat lymphocyte chromosomal aberration tests. There was no evidence of allergenic potential based on a comparison of the primary sequence of BD5088 with sequences in an allergen database. The enzyme was labile to pepsin digestion. Based on these data, BD5088 alpha-amylase preparation may be considered safe for use in food production such as corn wet milling.
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PMID:Safety evaluation of an alpha-amylase enzyme preparation derived from the archaeal order Thermococcales as expressed in Pseudomonas fluorescens biovar I. 1266 16

Lactoferricin (LFcin) was initially identified as an antimicrobial peptide derived by pepsin digestion of lactoferrin (LF), a multifunctional innate-defense protein in milk. Various synthetic analogs of LFcin have also been reported. LFcin inhibits a diverse range of microorganisms such as gram-negative bacteria, gram-positive bacteria, yeast, filamentous fungi, and parasitic protozoa, including some antibiotic-resistant pathogens. LFcin kills target organisms by membrane perturbation and acts synergistically with some antimicrobial agents. LFcin exhibits numerous biological activities in common with those of LF. Whereas LFcin suppresses the activation of innate immunity by microbial components such as lipopolysaccharide (LPS) and CpG DNA, the peptide itself activates immunity. Administration of LFcin analogs has been shown to protect the host via direct antimicrobial activity and immunostimulatory effects in several infection models of mice. Here we present a comprehensive review of investigations of LFcin and related peptides.
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PMID:Lactoferricin derived from milk protein lactoferrin. 1276 36

Human breast milk contains several proteins that supplement the newborn mucosal defense system and prevent gastrointestinal illnesses. One of these recently identified breast milk proteins is soluble CD14 (sCD14). By being an important component of the lipopolysaccharide (LPS) receptor complex, it has been suggested that breast milk sCD14 could stimulate the newborn immune system and help reduce gastrointestinal Gram-negative infections. However, to deliver its potential immune benefits to the neonate, sCD14 would have to survive the passage through the gastrointestinal tract and retain its biologic activity. We analyzed the presence of breast milk sCD14 in the neonatal digestive system and found breast milk sCD14 to be absent from the stools of breast-fed infants. In vitro digestion analysis with simulated gastric and pancreatic fluids revealed that sCD14 is likely to survive the pepsin digestion but is more prone to been nicked and digested by pancreatin. These findings suggest that the presence of intact breast milk sCD14 in the upper digestive system could promote innate immunity in this low bacteria density lumen. The low concentration of sCD14 in the LPS-rich environment of the distal gastrointestinal tract (i.e. commensal microflora) could prevent excessive inflammation.
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PMID:Killing the messenger in the nick of time: persistence of breast milk sCD14 in the neonatal gastrointestinal tract. 1649 74

Human CD14 plays an important role in innate immunity by being the key receptor of lipopolysaccharide found on Gram-negative bacteria. The recently discovered widespread localization of CD14 in secretions and mucosal surfaces reveals its extensive anti-microbial properties and numerous potential medical applications. To produce active recombinant human CD14 (rhCD14) for massive distribution, transgenic tobacco plants were successfully generated to express rhCD14 in the seed endosperm under the control of two versions (1.8 kb and 5.1 kb) of the rice glutelin Gt-1 promoter. Plant-made rhCD14 proteins reached a concentration of 16 microg/g of seeds and showed stability, proteolytic resistance to pepsin digestion and ability to induce the release of pro-inflammatory IL-6 and IL-8 cytokines in presence of LPS. The expression of plant rhCD14 in tobacco seeds constitutes a promising low-cost and abundant supply of this immune protein to further investigate its roles in, impacts on and potential medical applications for the innate immune system.
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PMID:Human CD14 expressed in seeds of transgenic tobacco displays similar proteolytic resistance and bioactivity with its mammalian-produced counterpart. 1660 57

Septicemia and endotoxemia initiated by bacterial lipopolysaccharide (LPS) are relatively common in suckling and weaned piglets. Maternal milk is a source of both nutrition and immune protection for piglets. Passive transfer of colostral antibodies is necessary for protection of neonatal piglets against diseases, but the concentration of immunoglobulins in milk rapidly declines during the 1st wk of lactation in all mammals. We hypothesized, therefore, that nonimmunoglobulin substances in milk contribute to the innate protection of neonates against septicemia during the suckling period. Using LPS-affinity chromatography for isolation of LPS-binding proteins and liquid chromatography-mass spectrometry for their identification, we identified in porcine milk the following proteins with LPS-binding capacity: lactoferrin, soluble CD14, serum amyloid A, alpha-S1 casein, beta-casein, and kappa-casein. For lactoferrin, alpha-S1 casein, and kappa-casein, in vitro pepsin digestion did not inhibit LPS-binding activity, whereas combined digestion with pepsin and pancreatin abolished it. The biologic functions of these LPS-binding proteins and peptides were not determined.
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PMID:Identification of lipopolysaccharide-binding proteins in porcine milk. 1704 75

Helicobacter pylori lipopolysaccharide (HP-LPS) is a potent virulence factor in the causation of gastric ulcer and gastritis. H. pylori-induced gastric pathology is prevalent throughout the world. Herbal medicines are attracting attention because of their traditional values, popularity and belief, as well as for their advantages such as less toxicity, affordability and medicinal value. The present study aimed to evaluate the anti-ulcer effect of a methanolic extract of Terminalia arjuna (TA) against HP-LPS-induced gastric damage in rats. Ulcers were induced with HP-LPS (50 mug per animal) administered orally daily for 3 days. The efficacy of TA on gastric secretory parameters such as volume of gastric juice, pH, free and total acidity, pepsin concentration, and the cytoprotective parameters such as protein-bound carbohydrate complexes in gastric juice and gastric mucosa was assessed. The protective effect of TA was also confirmed by histopathological examination of gastric mucosa. HP-LPS-induced alterations in gastric secretory parameters were altered favourably in rats treated with TA, suggesting that TA has an anti-secretory role. Furthermore, HP-LPS-induced impairments in gastric defence factors were also prevented by treatment with TA. These results suggest that the severe cellular damage and pathological changes caused by HP-LPS are mitigated by TA; these effects are comparable with those of sucralfate. The anti-ulcer effect of TA may reflect its ability to combat factors that damage the gastric mucosa, and to protect the mucosal defensive factors.
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PMID:Effect of methanolic extract of Terminalia arjuna against Helicobacter pylori 26695 lipopolysaccharide-induced gastric ulcer in rats. 1838 Sep 24


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