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)

Cytokines released from activated mononuclear leukocytes are involved in triggering the acute phase response and many of the inflammatory manifestations of ulcerative colitis and Crohn's disease. The ability of circulating monocytes from patients with ulcerative colitis and Crohn's disease to generate the cytokines interleukin 1 beta (IL 1 beta) and tumour necrosis factor alpha (TNF alpha), both spontaneously and in response to stimulation by lipopolysaccharide, was compared. IL 1 beta generation in response to lipopolysaccharide was significantly higher in Crohn's disease than in ulcerative colitis and normal controls, with a dramatic increase in patients with active disease. There was a significant reduction in lipopolysaccharide stimulated TNF alpha generation in ulcerative colitis patients compared with Crohn's disease and normal control subjects. IL 1 beta and TNF alpha release correlated significantly with serum C reactive protein and serum alpha 1 acid glycoprotein in Crohn's disease. The ability of conditioned medium from monocytes in Crohn's disease to enhance release of alpha 1 acid glycoprotein from the liver cell line HepG2 in culture was assessed. There was a significant positive correlation between TNF alpha and IL 1 beta presence in the supernatant and alpha 1 acid glycoprotein production. The differences in the cytokine profile in patients with Crohn's disease compared with ulcerative colitis suggest an intrinsic difference in the ability to produce cytokines in patients with these two forms of inflammatory bowel disease, and may explain features such as the enhanced ability to generate a brisk C reactive protein response in Crohn's disease.
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PMID:Peripheral blood monocyte cytokine production and acute phase response in inflammatory bowel disease. 162 58

The mRNAs of the CCAAT/enhancer-binding trans-activator proteins (C/EBPalpha and C/EBPbeta) serve as templates for the differential translation of several isoforms which have specific transcriptional regulatory functions. By using an oligonucleotide corresponding to the C/EBP binding site of the mouse alpha1-acid glycoprotein promoter, we detected multiple forms of C/EBPalpha and C/EBP++ beta proteins in the mouse liver that have DNA-binding activity. By using specific antisera, we detected C/EBPalphas with molecular masses of 42, 38, 30, and 20 kDa that have DNA-binding activity. The pool levels of the 42- and 30-kDa isoforms were high in control nuclear extracts and decreased significantly after lipopolysaccharide (LPS) treatment. The binding activity and protein levels of the 20-kDa isoform are low in controls and increase dramatically after LPS treatment. C/EBPbeta isoforms with molecular masses of 35, 20, and 16 kDa were also detected. The 35-kDa pool level did not change whereas the 20-kDa isoform was strongly induced in response to LPS. Western (immunoblot) and Southwestern (DNA-protein) analyses show that p42 C/EBPalpha forms specific complexes with the alpha1-acid glycoprotein oligonucleotide in control nuclear extract and that p20 C/EBP beta forms complexes in LPS-treated liver. Our studies suggest that synthesis of specific C/EBPalpha and C/EBPbeta isoforms occurred in the normal liver in vivo and that LPS mediated a differential initiation and inhibition of translation at specific AUG sites within each mRNA. The qualitative and quantitative changes in C/EBPalpha and C/EBPbeta isoform pool levels suggest that LPS or an LPS-stimulated factor can regulate the selection of AUG start sites for both activation and repression of translation. This regulation appears to involve an LPS-mediated down-regulation of initiation at the first AUG codon of the 42-kDa C/EBPalpha and dramatic translational up-regulation at the fifth AUG codon of the 20-kDa C/EBPalpha and the third AUG codon of the 20-kDa C/EBPbeta. These regulatory events suggest the existence of proteins that may act as translational trans-acting factors.
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PMID:Evidence for posttranscriptional regulation of C/EBPalpha and C/EBPbeta isoform expression during the lipopolysaccharide-mediated acute-phase response. 862 96

In the acute phase response to a variety of insults a rise in the levels of the acute phase proteins, including elevations of serum alpha 1 acid glycoprotein (AAG) occurs. The physiological role of AAG is unknown, however, the time course of AAG production in the acute phase response together with its strong affinity for basic compounds suggests that AAG may function as an immune modulator to bind both exogenous and endogenous inflammatory mediators. Using E. coli lipopolysaccharide (LPS), an initiator of the acute inflammatory response associated with septic shock, we demonstrate that AAG-LPS complexes can activate mouse macrophages in vitro. In a mouse animal model of sepsis, AAG was shown to protect against meningococcal endotoxin. To pursue the mechanism of AAG action we demonstrated that AAG interacts directly with LPS using dynamic light scattering particle sizing and particle mobility. We also determined the enthalpy of interaction of AAG and LPS and showed that AAG leads to agglutination of LPS impregnated rabbit red blood cells. These studies suggest that AAG may function as an immune-modulator in the acute phase response, possibly by counter-regulating the activity of macrophage pro-inflammatory cytokines.
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PMID:Alpha-1-acid (AAG, orosomucoid) glycoprotein: interaction with bacterial lipopolysaccharide and protection from sepsis. 917 23

The acute-phase protein (APP) response is regulated by cytokines such as interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor (TNF), but may also be influenced by malnutrition. The aims of this study were as follows: 1) to determine in rats the effect of a protein-deficient diet on IL-6 mRNA expression in intestine, liver and peripheral blood mononuclear cells (PBMC), and on alpha-1 acid glycoprotein (AGP) and alpha-2 macroglobulin (A2M) serum levels and hepatic mRNA expression; 2) to compare, in protein-deficient rats, the IL-6 and APP responses after a turpentine (TO)- or a lipopolysaccharide (LPS)-induced inflammation; and 3) to determine the effect of a protein malnutrition on IL-6 mRNA expression in rat PBMC treated ex vivo with LPS. Interleukin-6 mRNA was present in intestine and PBMC but not in the liver of malnourished rats, and was absent in any tissue or cells of controls. A2M was present in the serum from malnourished rats but not after refeeding. AGP mRNA expression was not influenced by protein malnutrition. In malnourished rats, IL-6 serum level peaked later than in controls after TO and LPS treatment. In malnourished TO-treated rats, A2M mRNA increased earlier than in controls and remained detectable later than in controls. AGP mRNA expression after TO was not influenced by protein malnutrition. In PBMC of malnourished rats, LPS-induced IL-6 mRNA expression occurred earlier and lasted longer than in controls. Our results indicate that protein malnutrition by itself induces IL-6 and A2M expression, and that it modulates the APP response to inflammation.
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PMID:Induction and modulation of acute-phase response by protein malnutrition in rats: comparative effect of systemic and localized inflammation on interleukin-6 and acute-phase protein synthesis. 944 38

We determined whether dietary ascorbic acid (0.3 or 3 g/kg diet) modulates hepatic microsomal mixed function oxidase (MFO) system and plasma alpha 1 acid glycoprotein (AGP) concentration in chicks treated with Escherichia coli lipopolysaccharide (LPS). Injection of LPS (250 micrograms/kg body weight every other day) intraperitoneally for 14 days decreased cytochromes P450 and b, content and NADPH-cytochrome c reductase activity in hepatic microsomes in male broilers. Content of cytochromes P450 and b5 was negatively correlated with plasma AGP concentration. Feeding ascorbic acid partly alleviated the reduction of cytochromes P450 and b5 in males. Plasma AGP concentration also increased with the LPS injection and was partly lowered by feeding ascorbic acid. The results indicate that dietary ascorbic acid modulates the responses of the microsomal MFO system and of plasma AGP concentration against repeated injection of LPS in male broiler chicks.
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PMID:Effect of dietary ascorbic acid on the hepatic microsomal mixed function oxidase system in liver of chicks treated with Escherichia coli lipopolysaccharide. 946 82

Mice are frequently used in models for the study of immunological processes related to inflammation. Since it is known that the degree of fucosylation of human acute phase proteins (APPs) is altered as a consequence of an inflammatory response, we have undertaken this study to gain more insight into the fucosylation of acute phase proteins as it occurs in mouse liver. Mice carrying the cluster of the three genes encoding human alpha1-acid glycoprotein (AGP), one of the well known APPs, were used and the fucosylation of AGP was assessed. A complete absence of fucosylation on the transgenic human AGP was found, which is in sharp contrast to AGP in human serum, of which a major proportion is normally alpha3-fucosylated. Remarkably, a large proportion of mouse AGP did contain fucose residues. Fucosylation was also detected on another APP, mouse protease inhibitor (PI). Alpha3-fucosylation of the transgenic human AGP can be achieved in vitro, using an alpha3/4-fucosyltransferase (alpha3/4-FucT) isolated from human milk, showing that the glycoprotein is not intrinsically resistant to fucosylation. Upon subsequent measurement of the activities of the possible fucosyltransferases present in liver membranes of parent and transgenic mice, only an N-linked-core alpha6-FucT and no alpha2-, alpha3- or alpha4-FucT activity was detected. This indicates that fucose residues found on the mouse serum proteins AGP and PI, which are synthesized in the liver, are most probably in alpha6-linkage to the core chitobiosyl unit. Interestingly, both alpha6- and alpha3-FucT activity was detectable in human liver membranes. None of the above mentioned findings were influenced by the induction of an acute phase response by administration of bacterial lipopolysaccharide. This study shows that: (a) alpha6-FucT is probably a protein specific-glycosyltransferase, since mouse AGP, but not human AGP, may be used as an acceptor; (b) in contrast to human liver, mouse liver does not express any alpha3-FucT-activity, thereby making the mouse incapable of producing the Sialyl Lewis(x) epitope on APPs, which is an important part of the inflammatory reaction in humans. This last finding indicates that the mouse is not suitable as a model for the study of those phenomena related to inflammation in humans, in which glycosylation of acute phase proteins could play a significant role.
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PMID:Sialyl Lewis(x) epitopes do not occur on acute phase proteins in mice: relationship to the absence of alpha3-fucosyltransferase in the liver. 961 26

The concentration of interleukin-6 (IL-6), alpha1-acid glycoprotein (alpha1-AG), and corticosterone (CORT) was investigated chronologically (0 h to 14 d) in the sera of 2-wk-old specific-pathogen-free chicks inoculated with Escherichia coli lipopolysaccharide (LPS). In the LPS group the IL-6 level was elevated from 1 h to 2 d and was the highest at 3 h. From 4 to 14 d the IL-6 level was low in the LPS group. In the PBS group, IL-6 was not detected except a mild increase from 1 h to 6 h. In the LPS group, the alpha1-AG level increased from 6 h to 4 d, and the peak was 2 d. In the PBS group the alpha1-AG level was always low. The CORT level in the LPS group was higher than that of PBS group at 1 h. This study suggests that E. coli LPS may elevate serum IL-6 and CORT, and that IL-6 and CORT may increase the alpha1-AG level in the chicks.
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PMID:Serum levels of interleukin-6, alpha1-acid glycoprotein, and corticosterone in two-week-old chickens inoculated with Escherichia coli lipopolysaccharide. 962 44

1. This study investigates whether previously documented effects of interleukin-4 in down-regulating pro-inflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from healthy individuals would be reproducible in PBMCs isolated from patients with multiple organ failure (acute disease model) and gastrointestinal cancer (chronic disease model). The effects of interleukin-4 on the ability of PBMC supernatants to elicit an acute phase protein response from isolated human hepatocytes were also studied. 2. Incubation of PBMCs with interleukin-4 significantly reduced both spontaneous and lipopolysaccharide-induced production of tumour necrosis factor and lipopolysaccharide-induced interleukin-6 production, demonstrating that the PBMCs from patients with acute and chronic disease are not refractory to the effects of interleukin-4. The effects of interleukin-4 on the ability of PBMCs from the groups studied to elicit an acute phase response were complex and varied both between patient groups and individual acute phase proteins. Overall, interleukin-4 reduced the potential of PBMCs to stimulate production of the positive acute phase proteins C-reactive protein, alpha1-antichymotrypsin and alpha1-acid glycoprotein.3. This work emphasizes the pleiotropic nature of cytokines and the complex regulatory mechanisms which exist. The study illustrates the difficulties in devising in vivo intervention strategies using cytokines such as interleukin-4.
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PMID:Effect of interleukin-4 on pro-inflammatory cytokine production and the acute phase response in healthy individuals and in patients with cancer or multiple organ failure. 973 Aug 55

Oncostatin M (OSM) is an interleukin-6 (IL-6) family cytokine known in particular to induce the synthesis of acute-phase proteins by hepatocytes. Because human polymorphonuclear neutrophils (PMN) can secrete numerous cytokines, the potential production of OSM by PMN was investigated. Highly purified PMN were found to contain an intracellular stock of preformed OSM that was rapidly mobilized by degranulating agents such as phorbol myristate acetate and granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, PMN produced OSM after a few hours of stimulation by various agonists. The most potent effect was observed with the combination of lipopolysaccharide and GM-CSF, which had a concentration- and time-dependent effect at both the protein and mRNA levels. Actinomycin D strongly reduced OSM mRNA induction, suggesting the involvement of gene transcription. Cycloheximide inhibited OSM protein synthesis but did not affect the release of preformed stores. In addition, OSM production was downregulated by dexamethasone, whereas IL-10 had no effect. The OSM produced by PMN was biologically active, as demonstrated by its ability to induce alpha1-acid glycoprotein synthesis by HepG2 cells. OSM secretion thus occurs through a two-step mechanism in PMN, consisting of early release of a preformed stock, followed by de novo protein synthesis. This would allow rapid and sustained OSM release to occur at inflammatory sites, and may contribute to the modulation of local inflammation.
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PMID:Oncostatin M production and regulation by human polymorphonuclear neutrophils. 994 86

Exchange in binding of transcription factors C/EBPalpha and C/EBPbeta at a regulatory site in the alpha1-acid glycoprotein (AGP) promoter, termed the acute phase response element (APRE), has been correlated with bacterial lipopolysaccharide (LPS) mediated induction. The APRE contains overlapping recognition sequences for C/EBP's and glucocorticoid receptor (GR). Electrophortetic mobility shift assays show that this site can bind both GR and C/EBP. However, using liver nuclear extract, which contains GR binding activity, only C/EBP binds to the APRE. Binding interference methods, using dimethyl sulfate and potassium permanganate modification of specific bases, detected interference only with modification of bases that are in the region of the C/EBP binding site that do not overlap with the GRE sequence. There are no significant differences between the interference patterns of control and LPS treated liver nuclear extracts, suggesting that the region of close contact between protein and DNA is similar for C/EBPalpha (untreated) and C/EBPbeta (treated).
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PMID:Interference mapping of nuclear protein binding to the acute phase response element of the mouse alpha1 acid glycoprotein gene. 1004 58


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