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)

Leucocytes (WBC) are recruited from peripheral blood into milk as part of the inflammatory response, mediated through cytokines or interleukins (IL) synthesized by mammary tissue and the milk somatic cells (SC). The inflammatory response is related to the concentration of SC and the cytokines produced. To investigate and to compare the kinetics of cytokine production in SC and WBC during inflammation, cell culture models were established, where SC and WBC were cultured in parallel (n = 3). In addition, macrophages or monocytes were isolated from milk and blood with antibody-coated magnetic beads and cultivated separately. Isolated cells were pure, unaltered and viable. Cultures were activated with 10 microg/ml lipopolysaccharide (LPS). After 0, 1, 2, 3, 4 and 8 h cells were harvested for RNA isolation. Cytokine [tumour necrosis factor alpha (TNFalpha), IL-1beta, IL-6] mRNA expression responses and transcriptional activity of CD14 and lactoferrin (LF) were quantified via a one-step real-time RT-PCR. Significant cytokine mRNA increases were found in all four cell culture types and genes, with peaks after 1 and 2 h (TNFalpha > IL-6 > IL-1beta). In WBC or monocytes higher LPS responses and longer persistence could be found than in corresponding milk cells (IL-1beta > IL-6 > TNFalpha). SC and macrophages are less responsive to LPS stimulation than WBC or monocytes. The strength of the immune response in the blood system is much more prominent than in the mammary gland. This may be ascribed to the role of CD14 on the cytokine production of the investigated cells, or may be caused by the blood-to-milk diapedesis. The constitutive transcription of CD14 mRNA in WBC and monocytes was found to be 6 to 15 times higher than in adequate milk cells.
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PMID:Short-term effects on pro-inflammatory cytokine, lactoferrin and CD14 mRNA expression levels in bovine immunoseparated milk and blood cells treated by LPS. 1610 97

It is known that lactoferrin is one of the functional proteins contained in mammalian milk and that it plays an important role in the immune system. In this study, we prepared multi-lamellar liposomal bovine lactoferrin composed of egg yolk phosphatidylcholine and phytosterol for oral delivery, and examined any resulting anti-inflammatory effects. Oral pretreatment of liposomal lactoferrin exhibited more suppressive effects than did non-liposomal lactoferrin on CCl4-induced hepatic injury in rats as well as on lipopolysaccharide-induced TNF-alpha production from mouse peripheral blood mononuclear leukocytes. Further investigation revealed that the liposomalization did not exert influence on the absorbability of lactoferrin to the venous blood or lymph following an intraduodenal administration in rats. Furthermore, there was no significant difference exhibited between the antigenicity of liposomal and non-liposomal lactoferrin, which was measured using the passive cutaneous anaphylaxis reaction following oral sensitization to them in guinea pigs. These results suggest that liposomal lactoferrin might act more effectively than conventional lactoferrin in the intestinal site, which is regarded as an active site of orally administered lactoferrin, although the biological mechanism is not fully understood yet. Consequently we propose that liposomal lactoferrin could be a novel active constituent useful for preventive and therapeutic treatment of inflammatory diseases.
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PMID:Liposomalization of lactoferrin enhanced it's anti-inflammatory effects via oral administration. 1614 46

Pathogenic microorganisms invading the mammary gland induce an inflammatory reaction which includes an increase of somatic cells in milk and activation of bacteriostatic enzymes and proteins in milk. During spontaneously occurring subclinical mastitis the somatic milk cells, mainly macrophages, secrete cytokines, eicosanoids, acute phase proteins and other immunomediators. In contrast, the bacteriostatic protein lactoferrin is mainly secreted by mammary epithelial tissue, while major milk proteins like alpha-lactalbumin and kappa-casein are down-regulated already during subclinical infection. Changes of the mRNA expression of various immunomediators in the mammary tissue of cows during 12 h after induction of mastitis via intramammary administration of lipopolysaccharide (LPS) in several studies are reported. Six healthy lactating cows were injected in one quarter with 100 microg Escherichia coli-LPS (O26: B6) and the contralateral quarter with saline (9 g/l) serving as control. mRNA expression in mammary biopsy samples of various inflammatory factors and milk proteins at 0, 3, 6, 9 and 12 h after LPS administration was quantified by real-time reverse transcription-PCR. In LPS-challenged quarters tumour necrosis factor alpha and cyclooxygenase-2 mRNA expression increased to their highest values (P<0.05) at 3 h after LPS-challenge. Expression of lactoferrin, lysozyme, inducible nitric oxide synthase, and of the apoptotic factors caspase-3, caspase-7 and FAS was elevated (P<0.05) and peaked at 6 h after challenge. No significant increase in mRNA expression of platelet-activating factor acethylhydrolase, 5-lipoxygenase, and insulin-like growth factor 1 was found. None of the parameters tested did change significantly in the control quarters. mRNA expression of major milk proteins did not change significantly in response to the LPS challenge (alphaS1-casein, alphaS2-CN, beta-CN and beta-lactoglobulin) except for alpha-lactalbumin which decreased (P<0.05) in LPS-treated and control quarters and for kappa-CN which decreased in the LPS-treated quarters. In conclusion, mRNA expression of the majority albeit not all inflammatory factors changed within hours of LPS challenge. Decreased gene expression of alpha-lactalbumin and kappa-CN may reduce milk yield and suitability for cheese production.
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PMID:Gene expression of factors related to the immune reaction in response to intramammary Escherichia coli lipopolysaccharide challenge. 1618 Jul 30

We previously demonstrated that lactoferrin inhibits adherence of enteropathogenic Escherichia coli to HEp-2 cells and decreases invasiveness of Shigella flexneri in HeLa cells by disruption of the type III secretory system (TTSS) of both enteropathogens. To determine whether these effects were specific to the TTSS, we assessed the activity of bovine lactoferrin on enteroaggregative E. coli (EAEC), enteropathogens whose virulence is not TTSS dependent. Bovine lactoferrin at a concentration of 1.0 and 0.1 mg/mL inhibited EAEC growth. Saturation with iron reversed the bacteriostatic effect. Lactoferrin under nonbacteriostatic conditions decreased EAEC adherence to HEp-2 cells as evaluated by microscopy and CFUs; this effect was not iron dependent. Lactoferrin inhibited EAEC biofilm formation and increased autoagglutination. Lactoferrin blocks EAEC adherence by inducing release and degradation of aggregative adherence fimbria, a key element of EAEC pathogenesis. We hypothesized that lactoferrin binding to lipid A of lipopolysaccharide disrupts the virulence proteins anchored to the bacterial outermembrane. These data suggest that the effect of lactoferrin on surface proteins is not restricted to organisms having a TTSS.
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PMID:Effect of lactoferrin on enteroaggregative E. coli (EAEC). 1693 9

This is the first study describing an experimental mastitis model using transgenic cows expressing recombinant human lactoferrin (rhLf) in their milk. The aim of the study was to investigate the concentrations in milk and protective effects of bovine and recombinant human lactoferrin in experimental Escherichia coli mastitis. Experimental intramammary infection was induced in one udder quarter of seven first-lactating rhLf-transgenic cows and six normal cows, using an E. coli strain isolated from cows with clinical mastitis and known to be susceptible to Lf in vitro. Clinical signs were recorded during the experimental period, concentrations of human and bovine Lf and indicators of inflammation and bacterial counts were determined for milk, and concentrations of acute-phase proteins and tumor necrosis factor alpha were determined for sera and milk. Serum cortisol and blood hematological and biochemical parameters were also determined. Expression levels of rhLf in the milk of transgenic cows remained constant throughout the experiment (mean, 2.9 mg/ml). The high Lf concentrations in the milk of transgenic cows did not protect them from intramammary infection. All cows became infected and developed clinical mastitis. The rhLf-transgenic cows showed milder systemic signs and lower serum cortisol and haptoglobin concentrations than did controls. This may be explained by lipopolysaccharide-neutralizing and immunomodulatory effects of the high Lf concentrations in their milk. However, Lf does not seem to be a very efficient protein for genetic engineering to enhance the mastitis resistance of dairy cows.
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PMID:Transgenic cows that produce recombinant human lactoferrin in milk are not protected from experimental Escherichia coli intramammary infection. 1695 96

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

A basic challenge in the treatment of septic patients in critical care units is the release of bacterial pathogenicity factors such as lipopolysaccharide (LPS, endotoxin) from the cell envelope of Gram-negative bacteria due to killing by antibiotics. LPS aggregates may interact with serum and membrane proteins such as LBP (lipopolysaccharide-binding protein) and CD14 leading to the observed strong reaction of the immune system. Thus, an effective treatment of patients infected by Gram-negative bacteria must comprise beside bacterial killing the neutralization of endotoxins. Here, data are summarized for synthetic compounds indicating the stepwise development to very effective LPS-neutralizing agents. These data include synthetic peptides, based on the endotoxin-binding domains of natural binding proteins such as lactoferrin, Limulus anti-LPS factor, NK-lysin, and cathelicidins or based on LPS sequestering polyamines. Many of these compounds could be shown to act not only in vitro, but also in vivo (e.g. in animal models of sepsis), and might be useful in future clinical trials and in sepsis therapy.
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PMID:Mechanisms of endotoxin neutralization by synthetic cationic compounds. 1705 90

Neutrophils enter tissues including the uterus and are found in the endometrium in increased numbers prior to menses. In this environment, they are exposed to transforming growth factor (TGF)-beta1 produced by endometrial stromal and epithelial cells. We observed that incubation of neutrophils in vitro with TGF-beta1 at 1 pg/ml significantly reduced their secretion of lactoferrin in response to lipopolysaccharide (LPS). This effect was achieved with as little as 15 min of pretreatment with TGF-beta1. Inhibition of lactoferrin release by TGF-beta1 was observed irrespective of whether neutrophils were stimulated by ligands for Toll-like receptor (TLR)-2, TLR-4 or FPR, the G protein-coupled receptor for formylated peptides. Inhibition by TGF-beta1 was negated by SB-431542, a small molecule inhibitor that specifically blocks the kinase activity of the type I TGF-beta receptor (ALK5) In contrast to lactoferrin release, another important neutrophil function, interleukin (IL)-8 driven chemotaxis, was not affected by TGF-beta1 at 1 pg/ml or 100 pg/ml. We conclude that in tissues of the female reproductive tract, TGF-beta1 inhibition of neutrophil degranulation may prevent these cells from initiating an inflammatory response or releasing degradative enzymes that could potentially damage the oocyte or fetus.
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PMID:Inhibition of human neutrophil degranulation by transforming growth factor-beta1. 1740 59

Lactoferrin (Lf), an iron-binding multifunctional glycoprotein, is abundantly present in colostrum and milk of different species such as humans, bovines, and mice. Our previous observation revealed that bovine colostral Lf is transported into the systemic circulation and cerebrospinal fluid from gut-lumen through receptor-mediated transcytosis in calves. Diarrhea caused by Escherichia coli is one of the important causes of infant morbidity and mortality in developing countries. We investigated the effects of bovine lactoferrin (BLf) on lipopolysaccharide (LPS)-induced diarrheogenic activity, gastrointestinal transit (GIT), and intestinal fluid content in mice. LPS accumulated abundant fluid in the small intestine in a dose-dependent manner, induced diarrhea, but decreased the GIT. Pretreatment with BLf significantly attenuated the effects of LPS on the diarrheogenic activity and intestinal content, but reversed the GIT when compared with NG-nitro-L-arginine-methyl ester (L-NAME, a non-selective NOS inhibitor) or indomethacin (an inhibitor of prostaglandin synthesis). Both plasma NO and PGE2 in enterocytes were found to increase in LPS-treated mice and were reversed by BLf. These findings demonstrate that the action of BLf against LPS was specific and it exerts antidiarrheal activity through modulating the cyclooxygenase [NO and PGE2] pathway in the gut.
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PMID:Bovine lactoferrin protects lipopolysaccharide-induced diarrhea modulating nitric oxide and prostaglandin E2 in mice. 1748 61

Lactoferrin (LF) is a multifunctional protein. While its functions and mechanism of actions are actively being investigated, the cellular signals that regulate LF expression have not been as explored. We have previously demonstrated that LF is upregulated by estrogen in the reproductive system. In this study, we show that the expression of LF was stimulated by bacterial lipopolysaccharide (LPS) and double-stranded RNA (dsRNA) in normal mouse mammalian HC-11 cells. When cells were exposed to either LPS or dsRNA, the mRNA and protein of LF were increased in a dose- and time-dependent manner, yet the kinetics of LF induction by dsRNA or LPS were different. The LPS and dsRNA-induced LF was mainly released into the culture medium where it blocked TNF-alpha production in exposed cells. We explored the mechanisms of LF induction by LPS and dsRNA using specific inhibitors and found that the induction could be attenuated by inhibitors to PKC, NF-kappaB, p38 and JNK, but not by an inhibitor to PKA. Interestingly, ERK inhibitor was effective against dsRNA but not against LPS induction of LF. These data suggest that LF was induced by LPS and dsRNA through PKC, NF-kappaB and MAPK pathways which in turn play an inhibitory role in the continuation of innate inflammation.
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PMID:Induction of lactoferrin gene expression by innate immune stimuli in mouse mammary epithelial HC-11 cells. 1853 95


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