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)

A number of altered immunologic responses to lipopolysaccharide (LPS) in C3H/HeJ mice result from the expression in B lymphocytes of a defective genetic locus, termed Lps. Lps has been mapped to chromosome 4 between two loci, Mup-1 and Ps. As it is difficult to type individual mice for LPS responsiveness in more than one type of assay, we have utilized Mup-1 as a genetic marker to correlate LPS responses in mice to the expression of the Lps locus. Three nonlymphoid responses to LPS have been examined in 12 recombinant inbred strains of mice and in a backcross linkage analysis, and are all regulated by the expression of the Lps locus. These responses are hypothermal changes in body temperature, and the elevation in serum levels of a colony stimulating factor and the precursor of the secondary amyloid protein AA. Therefore, the initiation of LPS responses in different cell types in mice involve the expression of a common locus. These linkage studies provide a means for analyzing the genetic control of many of the diverse reactions of the endotoxic response to LPS.
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PMID:Genetic control of endotoxic responses in mice. 34 67

The serum precursor SAA of the secondary amyloid protein AA has been detected by solid-phase radioimmunoassay as a normal serum alpha-globulin of mol wt 160,000, which dissociates to a more stable 12,500 dalton moiety on treatment with formic acid. In 12 strains of mice, including T-cell-deficient nude mice, treated with the amyloid-inducing agents lipopolysaccharide (LPS) or casein, SAA behaved as an acute-phase reactant. SAA concentration rose to about 750 mug/ml by 24 h and returned to less than 1 mug/ml by 48 h. Since the amyloid-resistant colchicine-treated mice and AJ mice had a normal SAA response to LPS, it appears that their resistance to amyloid induction is due to the nature of their SAA processing rather than decreased SAA production. C3H/HeJ mice, which have defective B-lymphocyte responses to LPS, required extremely high dosages of LPS to cause SAA elevation, although their SAA response to casein was normal. This suggests that SAA is an acute-phase protein produced as a result of B-lymphocyte stimulation. Preliminary evidence suggests that at the height of an acute SAA response, liver homogenates are particularly rich in protein AA cross-reacting material.
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PMID:Murine model for human secondary amyloidosis: genetic variability of the acute-phase serum protein SAA response to endotoxins and casein. 97 36

The nucleotide sequences of two mink serum amyloid A (SAA) cDNA clones have been analyzed, one (SAA1) 776 base pairs long and the other (SAA2) 552 base pairs long. Significant differences were discovered when derived amino acid sequences were compared with data for apoSAA isolated from high density lipoprotein. Previous studies of mink protein SAA and amyloid protein A (AA) suggest that only one SAA isotype is amyloidogenic. The cDNA clone for SAA2 defines the "amyloid prone" isotype while SAA1 is found only in serum. Mink SAA1 has alanine in position 10, isoleucine in positions 24, 67, and 71, lysine in position 27, and proline in position 105. Residue 10 in mink SAA2 is valine while arginine and asparagine are at positions 24 and 27, respectively, all characteristics of protein AA isolated from mink amyloid fibrils. Mink SAA2 also has valine in position 67, phenylalanine in position 71, and amino acid 105 is serine. It remains unknown why these six amino acid substitutions render SAA2 more amyloidogenic than SAA1. Eighteen hours after lipopolysaccharide stimulation, mink SAA mRNA is abundant in liver with relatively minor accumulations in brain and lung. Genes encoding both SAA isotypes are expressed in all three organs while no SAA mRNA was detectable in amyloid prone organs, including spleen and intestine, indicating that deposition of AA from locally synthesized SAA is unlikely. A third mRNA species (2.2 kilobases) was identified and hybridizes with cDNA probes for mink SAA1 and SAA2. In addition to a major primary translation product (molecular mass 14,400 Da) an additional product with molecular mass 28,000 Da was immunoprecipitable.
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PMID:Mink serum amyloid A protein. Expression and primary structure based on cDNA sequences. 235 48

Serum amyloid A (SAA) is a small (12 kDa) acute-phase apoprotein of high density lipoprotein found in mammals. It is also the precursor to amyloid protein A, the main protein constituent of fibrils found in amyloidosis secondary to chronic or recurrent inflammation--e.g., rheumatoid arthritis. However, rats do not develop amyloidosis and SAA is not an apoprotein of rat high density lipoprotein; thus rats appear to be an exception in regard to expression of SAA genes. We report here that rats do have representatives of the SAA gene family and express two distinct SAA mRNAs. Moreover, the pattern of genes expressed among tissues, and their induction by inflammatory agents, is similar to that of related mouse genes. RNA from various tissues of normal and injured rats was examined by RNA blot hybridization with SAA cDNA and complementary RNA probes for the three murine SAA genes. A SAA mRNA of approximately 400 nucleotides related to mouse SAA1 and SAA2 mRNAs reached a high level in liver 24 hr after injection of bacterial lipopolysaccharide. No extra-hepatic tissues were found to express the SAA1/SAA2-related mRNA. Turpentine induced two hepatic SAA1/SAA2-related mRNAs of approximately 400 and approximately 500 nucleotides in length. Liver SAA1/SAA2-related mRNA hybrid selected and translated in a wheat germ protein-synthesizing system, from lipopolysaccharide- and turpentine-injected rats, produced a single protein with an estimated molecular mass of 8 kDa. This rat liver SAA-related mRNA appears to lack a highly conserved coding region for portions of two amphipathic helical domains and the joining sequence. An mRNA related to mouse SAA3 was found expressed at a high level in lung after lipopolysaccharide but not following turpentine injection. This mRNA was also expressed at high levels in ileum and large intestine of control rats and was not found in the liver of control or challenged rats. These observations show that the SAA gene family is present and expressed in rats and that its expression is found under situations similar to those found in mice. This lends support for the importance of the SAA gene family in the response to injury by vertebrates.
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PMID:Rat tissues express serum amyloid A protein-related mRNAs. 292 11

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

This study has evaluated the relationship between tumor growth and induction of acute-phase proteins. It has also determined whether an intact cellular immunity is obligatory for a fully expressed acute-phase plasma protein response in the presence of a highly antigenic tumor. Quantitatively, acute-phase responses (protein synthesis, plasma concentrations, hepatic RNA content, anorexia) were proportional to tumor burden. Anti-inflammatory drugs (indomethacin 1 micrograms/g body wt, dexamethasone 0.5 micrograms/g body wt) had no direct effect on the attenuation of the systemic acute-phase responses, but did affect them indirectly by decreasing tumor growth. Immune suppression (cyclosporine A at 20 or 60 micrograms/g body wt) had no effect on either acute-phase reactions or local tumor growth. In endotoxin-stimulated (lipopolysaccharide) normal mice, immune suppression aggravated anorexia and caused high mortality, while dexamethasone partly reversed these effects in endotoxin-stimulated mice. Plasma levels of acute-phase proteins correlated to circulating levels of IL-6 in untreated tumor-bearing mice, but this relationship was not obvious in either drug-treated tumor-bearing or endotoxin-stimulated mice. Tumor tissue induced the synthesis of different acute-phase proteins compared to endotoxin. However, disintegrated normal liver tissue induced the synthesis of serum amyloid protein to the same extent as the growing tumor. This effect was primarily associated with the mitochondrial/lysosomal and microsomal liver cell fractions. In conclusion, the overall acute-phase protein response is not a modulating factor of tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute-phase proteins in response to tumor growth. 750 21

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

SB 203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4- pyridyl)imidazole], a selective cytokine suppressive binding protein/p38 kinase inhibitor, was evaluated in several models of cytokine inhibition and inflammatory disease. It was demonstrated clearly to be a potent inhibitor of inflammatory cytokine production in vivo in both mice and rats with IC50 values of 15 to 25 mg/kg. SB 203580 possessed therapeutic activity in collagen-induced arthritis in DBA/LACJ mice with a dose of 50 mg/kg resulting in significant inhibition of paw inflammation and serum amyloid protein levels. Antiarthritic activity was also observed in adjuvant-induced arthritis in the Lewis rat when SB 203580 was administered p.o. at 30 and 60 mg/kg. Evidence for disease-modifying activity in this model was indicated by an improvement in bone mineral density and by histological evaluation. Additional evidence for beneficial effects on bone resorption was provided in the fetal rat long bone assay in which SB 203580 inhibited 45Ca release with an IC50 of 0.6 microM. In keeping with the inhibitory effects on lipopolysaccharide-induced tumor necrosis factor-alpha in mice, SB 203580 was found to reduce mortality in a murine model of endotoxin-induced shock. In immune function studies in mice treated with SB 203580 (60 mg/kg/day for 2 weeks), there was some suppression of an antibody response to ovalbumin, whereas cellular immune functions measured ex vivo were unaffected. This novel profile of activity strongly suggests that cytokine inhibitors could provide significant benefit in the therapy of chronic inflammatory disease.
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PMID:Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function. 896 71

Polymyxin B, a cationic cyclic decapeptide antibiotic, is well known to bind endotoxin and to neutralize its toxicity. Based on this principle, polymyxin B was immobilized on the chloroacetamidomethylated polystyrene fiber that is reinforced by polypropylene. The adsorbing capacity of the obtained fibers (polymyxin B immobilized fiber [PMX-F]) was evaluated on endotoxin and other serum components in serum and on heparin in phosphate-buffered saline. Fluorescein isothiocyanate-labeled or tetramethylrhodamine isothiocyanate-labeled lipopolysaccharide (LPS) was used as endotoxin. The measurement of the fluorescence intensity showed that PMX-F adsorbed these LPSs depending on their concentration and on amount. The adsorption of endotoxin was confirmed by desorption of LPS from PMX-F as well. PMX-F adsorbed serum amyloid protein A besides LPS, but neither C-reactive protein nor low-density lipoprotein. The adsorbing property of heparin was low.
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PMID:Removal of endotoxin in blood by polymyxin B immobilized polystyrene-derivative fiber. 1198 49


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