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 ability of steroids to modulate the appearance of Interleukin-1(IL-1) in vivo was evaluated in a model of endotoxin shock. High levels of IL-1 were found in serum from A/J mice which were sensitized with P. acnes and challenged with bacterial lipopolysaccharide (LPS). The factor appeared in the serum 2-4 hours after LPS challenge and was dependent on the period of P. acnes sensitization and the dose of LPS. Treating the mice with dexamethasone prior to LPS challenge resulted in significantly lower thymocyte proliferative activity in the serum. Three experiments demonstrated that this reduced activity reflects a decrease in IL-1. 1) The reduced activity was not due to the presence of proliferation inhibitors since mixing the serum from dexamethasone-treated mice with purified IL-1 or adding the equivalent amount of steroid directly to thymocyte cultures did not reduce the degree of proliferation. 2) When the serum was fractionated by gel filtration, the proliferative activity for both control and steroid treated sera eluted at 10-16 kilodaltons; however, the activity was nearly 50% less in the sample from steroid-treated mice. 3) In addition to thymocyte proliferative activity, IL-1 induces an increase in the serum titer of the acute phase protein known as serum amyloid A. Both serum- and gel-purified samples were able to induce the SAA, but again the samples from steroid-treated mice were much less active. We conclude that the factor produced in vivo has the properties of IL-1 and that the serum titre of the factor is reduced by dexamethasone treatment.
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PMID:Reduction of serum Interleukin-1-like activity after treatment with dexamethasone. 387 68

Experimental amyloidosis was induced in mice by intraperitoneal injections of endotoxin (lipopolysaccharide (LPS)). In addition to LPS, a group of mice received high-density lipoprotein (HDL)-SAA complexes isolated from human acute-phase serum, whereas a group of control mice received saline in addition to LPS. Isolated amyloid fibrils from the mice given HDL-SAA contained human AA protein, as shown by immunodiffusion, immunoblot, and enzyme-linked immunosorbent assay techniques, in addition to mouse AA. In contrast, amyloid from the control mice contained exclusively AA of mouse origin. Thus, the experiments provided solid evidence that SAA is the precursor for amyloid fibril protein AA.
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PMID:Transformation of amyloid precursor SAA to protein AA and incorporation in amyloid fibrils in vivo. 392 50

The serum amyloid protein (apo-SAA) is a unique high density lipoprotein apoprotein exhibiting dramatic increases in plasma concentration following host injury. The events involved in the secretion of apo-SAA and assembly of apo-SAA-rich lipoprotein particles were studied in primary, serum-free culture of adult BALB/c mouse hepatocytes harvested 3 h following administration of the potent apo-SAA inducer, bacterial endotoxin (50 micrograms of intraperitoneally administered Salmonella typhosa lipopolysaccharide). An approximately 3.5-fold increase in the initial rate of apo-SAA secretion was observed over that of hepatocytes isolated from control mice, whereas the rate of apo-A-I secretion was unchanged by endotoxin administration. Sodium dodecyl sulfate-gel electrophoresis and autoradiography of [35S]methionine-labeled cell products indicated the synthesis of both major mouse apo-SAA isotypes by hepatocytes. Essentially all of the secreted apo-SAA chromatographed in Sephadex G-150 with an elution volume corresponding to a molecular weight of approximately 12,000. Approximately 90% of the secreted apo-SAA was recovered in fractions (d greater than 1.21 g/ml) following ultracentrifugal fractionation. In media supplemented with human lipoproteins (100 micrograms/ml), approximately 50% of the secreted apo-SAA was recovered in the high density lipoprotein fraction. These results suggest that mouse apo-SAA is secreted in monomeric form and becomes associated with lipoproteins in the intravascular compartment.
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PMID:Secretion of serum amyloid protein and assembly of serum amyloid protein-rich high density lipoprotein in primary mouse hepatocyte culture. 680 50

Bacterial endotoxin is a potent inducer of the serum amyloid protein (apo-SAA), a high density lipoprotein (HDL) apoprotein. In a study of the induction of apo-SAA and the structure of apo-SAA-rich lipoprotein particles in mice, we have observed that, following intraperitoneal administration of Salmonella typhosa lipopolysaccharide (50 micrograms), plasma apo-SAA levels rose from base-line levels of less than 1% to greater than 20% of the HDL protein content at 20 h postinjection. No changes in the relative content of other HDL apoproteins were noted; analysis of apo-SAA-rich HDL lipid content indicated a significant decrease (10%) in phospholipid content relative to that of control HDL. Two major apo-SAA isotypes, apo-SAA1 and apo-SAA2, were identified, having apparent molecular weights of 12,600 and 11,800, respectively, and isoelectric points of 6.35 and 6.20, respectively. Quantitative immunoprecipitation experiments indicated that essentially all of the apo-SAA was bound to lipoprotein particles containing apo-A-I. Apo-SAA was distributed among higher density HDL subfractions than were other HDL apoproteins following density gradient centrifugation, and subfractions having apo-SAA:apo-A-I molar ratios of greater than 2:1 were identified. These results indicate the formation of a subset of apo-SAA-rich HDL particles following apo-SAA induction by endotoxin.
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PMID:Changes in high density lipoprotein content following endotoxin administration in the mouse. Formation of serum amyloid protein-rich subfractions. 710 14

Inbred CE/J mice have been identified as extremely resistant to azocasein-induced amyloidosis relative to five commonly used inbred strains, A/J, CBA/J, C57BL/6J, C3H/HeN, and SJL/J. The enhanced amyloid resistance in CE/J mice seems to derive from the novel structure of the SAA gene family in CE/J mice, as determined by Southern blot hybridization analysis of SAA gene structure and isoelectric focusing analysis of acute phase SAA proteins in the six inbred strains. In CE/J mice, a single, novel SAA isoform of pI 6.15 is present, whereas in the other strains the amyloidogenic SAA2 isoform (pI 6.3) is codominantly expressed with SAA1 (pI 6.45). Two other inbred strains, PERU and IS/CAM, share common SAA specific HindIII DNA fragments with CE/J mice. Wild-derived Mus musculus mice differ from all of the inbred strains studied, both in SAA gene structure and in the pattern of SAA isoform production; two isoforms, one pI 6.15 and the other pI 6.3 (corresponding to SAA2), were codominantly expressed. Only the pI 6.15 isoform, not SAA1 and 2, was produced by CE/J mice in response to lipopolysaccharide, casein, silver nitrate, interleukin-1, or tumor necrosis factor; tumor necrosis factor was a weaker stimulus than interleukin-1 for the pI 6.15 isoform as it is for SAA1 and 2 production in the other inbred strains. This study provides a new line of evidence supporting the role of precursor structure as a determining factor in murine amyloid A amyloidosis and provides a valuable model for studies of amyloidogenesis.
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PMID:Characterization of the inbred CE/J mouse strain as amyloid resistant. 790 95

Two-dimensional electrophoresis was used to study SAA and AA proteins in mink during lipopolysaccharide-induced inflammation and amyloidogenesis. Three isotypes, SAA pI 6.8 and SAA pI 6.5 (both SAA1-like), and SAA pI 6.0 (SAA1- and SAA2-like), were identified in serum after both single and multiple LPS injections. Total SAA serum levels were highest in the early phase of induction, followed by a decrease ranging from 1 to 50% of the peak value during the rest of the experiment. The variation in the total SAA levels correlated with the total SAA mRNA levels. Low total SAA levels were seen both in non-amyloidotic and amyloidotic animals, and a general decrease of all isotypes was demonstrated. In hepatic amyloid fibrils, several AA isotypes, with amino acid sequence homologous exclusively to that of SAA2, were found. In the corresponding splenic material, fragments of histones H2A and H2B constituted most of the low molecular mass proteins, and no protein AA was detected. In spite of low serum levels and a non-specific isotype removal, the results confirm that SAA2 is amyloidogenic in mink.
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PMID:Serum amyloid A protein in mink during endotoxin induced inflammation and amyloidogenesis. 809 Nov 33

Serum amyloid A (SAA) is an acute-phase plasma protein which increases up to 1000-fold after an acute-phase stimulus. Several SAA genes and corresponding protein isotypes exist in individual species. Liver is the main source of production, but extra-hepatic SAA expression has been described. In this study inflammation was induced in rabbits with lipopolysaccharide, turpentine, or casein. Transcription of SAA mRNA was studied using Northern blot analysis with probes specific for three different rabbit SAA isotypes and analysed by scanning densitometry. In the stimulated liver slight variation in SAA mRNA transcription level was seen after stimulation with different inflammatory agents. After lipopolysaccharide-stimulation SAA gene expression was also seen in most of the extra-hepatic organs. After turpentine stimulation SAA mRNA was seen in the liver, the ovary, and the small intestines, and after casein stimulation only in the liver and the ovary. SAA1 and SAA2 were induced exclusively in the liver, while SAA3 was induced mainly in the extra-hepatic organs. This indicates that the SAA genes probably are independently regulated both in relation to stimulus, gene- and tissue-specificity.
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PMID:Differential expression of rabbit serum amyloid A genes in response to various inflammatory agents. 823 44

Serum amyloid A (SAA) is an acute phase protein and the precursor of amyloid protein A (AA) in deposits of secondary amyloidosis. Several isotypes exist in mink, but previous studies suggest that mink AA is derived from only one. To assess the effect of repeated episodes of inflammation and induction of amyloidosis, qualitative and quantitative changes in hepatic and extrahepatic SAA mRNA were studied. Young female mink received subcutaneous lipopolysaccharide injections for amyloid induction. Studies were performed using RNA probes and oligonucleotide probes specific for each of two SAA mRNA species. Northern blot hybridization showed that hepatic SAA1 and SAA2 mRNA levels increased dramatically after inflammatory stimulation, and were subsequently maintained at elevated levels, showing considerable interindividual variation, but only a slight decrease during repeated inflammatory stimuli and the early stages of amyloid deposition. No preferential accumulation of mRNA specifying a particular isotype was found during the experiment. Differential expression of mink SAA mRNA during repeated inflammatory stimulation does not seem to explain why only SAA2-derived AA is found in amyloid deposits. Extrahepatic SAA mRNA seemed to be independently regulated and may thus represent another, yet not characterized, SAA isotype.
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PMID:Expression of serum amyloid A genes in mink during induction of inflammation and amyloidosis. 826 20

We have investigated the differential regulation of the mouse (Balb/c) acute phase reactants, alpha 1-acid glycoprotein and serum amyloid A by heavy metals (Hg, Cd, Pb, Cu, Ni and Zn). Mice have two distinct alpha 1-acid glycoprotein mRNAs encoded by alpha 1-acid glycoprotein gene-1, (AGP-1) and alpha 1-acid glycoprotein gene-2 (AGP-2) and 3 distinct serum amyloid A mRNAs encoded by serum amyloid A gene-1, (SAA-1), serum amyloid A gene-2 (SAA-2) and serum amyloid A gene-3 (SAA-3). Using specific oligonucleotides as probes we have demonstrated that the AGP-1 and AGP-2 genes, and the SAA-1 and SAA-2 genes are differentially induced by heavy metals in the liver. At the peak of induction, AGP-2 mRNA is 80-100-fold higher than the AGP-1 mRNA level; the SAA-1 mRNA level is approx. 40-fold higher than SAA-2, and SAA-3 mRNA is not detected. A similar differential pattern of expression is observed in bacterial lipopolysaccharide mediated inductions. However, low levels of SAA-3 are also seen in this treatment. Adrenalectomy has no effect on the inductions by heavy metals of AGP-2 and the SAAs, indicating that the glucocorticoid receptor pathway may not function in this regulation. However, AGP-1 induction is significantly delayed, indicating that glucocorticoid may be essential for a rapid response to Hg. The liver is the major site of heavy metal induction of AGP and SAA genes; Hg induces AGP-1 and 2, and SAA-1 and 2 only in the liver. Our studies clearly show that the AGP and SAA genes belong to a subgroup of acute-phase reactants that respond to heavy metals. CRP is another member of this family. Furthermore, our data suggest that the mechanism is not directly mediated by glucocorticoid or cytokine induction pathways.
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PMID:The differential induction of alpha 1-acid glycoprotein and serum amyloid A genes by heavy metals. 835 29

Serum amyloid A (SAA) is an acute-phase plasma protein which increases 100- to 1000-fold in response to inflammatory stimuli. In this study pregnant rabbits were subjected to laparotomy and their fetuses were injected with lipopolysaccharide (LPS) or various cytokines. Newborn rabbits were likewise stimulated. Hepatic SAA mRNA was studied using Northern blot analyses and scanning densitometry. In vitro derived RNA was used as standard for quantitative mRNA analyses. Cytokine concentrations in amniotic fluid and serum were analysed by biological assays. Fetal rabbits responded to cytokine stimulation by increased hepatic SAA mRNA expression, both during late gestation and in the early neonatal period. However, differences in dose-responses, kinetics and mRNA concentrations were seen dependent on gestational age. IL-1 and tumour necrosis factor (TNF) induced hepatic accumulation of both SAA1, SAA2 and SAA3, while only SAA1 and SAA2 mRNA accumulation was seen after IL-6 stimulation. High levels of IL-1 and TNF found in amniotic fluid from LPS-stimulated fetal rabbits corresponded with high levels in fetal, but not in maternal, serum. High levels of IL-1 and TNF, but no IL-6, were seen in newborn control sera and in adult serum 1 day after a normal delivery. The study details the complexity of the cytokine-induced in vivo response of SAA mRNA in fetal and neonatal rabbits.
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PMID:Cytokine-induced differential expression of serum amyloid A genes in fetal and neonatal rabbits. 856 21


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