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)

Eosinophil-derived cationic proteins play an essential role in the pathogenesis of bronchial asthma. We tested whether cationic proteins interfere with the cationic amino-acid transport in alveolar macrophages (AMPhi) and tracheal epithelial cells, and whether L-arginine-dependent pathways were affected. The effect of cationic polypeptides on cellular uptake of [(3)H]-L-arginine, nitrite accumulation, and the turnover of [(3)H]-L-arginine by nitric oxide (NO) synthase and arginase (formation of [(3)H]-L-citrulline and [(3)H]-L-ornithine, respectively) were studied. Poly-L-arginine reduced [(3)H]-L-arginine uptake in rat AMPhi and tracheal epithelial cells in a concentration-dependent manner (at 300 microgram/ml by 70%). Poly-L-lysine, protamine, and major basic protein (each up to 300 microgram/ml) tested in rat AMPhi inhibited [(3)H]-L-arginine uptake by 35 to 50%. During 6 h incubation in amino acid-free Krebs solution, rat AMPhi, precultured in the absence or presence of LPS (1 microgram/ml), accumulated 1.4 and 3.5 nmol/10(6) cells nitrite, respectively. Addition of 100 microM L-arginine increased nitrite accumulation by 70 and 400% in control and lipopolysaccharide-treated AMPhi, respectively. Nitrite accumulation in the presence of L-arginine was reduced by poly-L-arginine and poly-L-lysine (100 and 300 microgram/ml) by 60 to 85% and 20 to 30%, respectively. Poly-L-arginine, but not poly-L-lysine, inhibited nitrite accumulation already in the absence of extracellular L-arginine. Poly-L-arginine (300 microgram/ml) inhibited [(3)H]-L-citrulline formation by AMPhi stronger than that of [(3)H]-L-ornithine. We conclude that cationic proteins can inhibit cellular transport of L-arginine and this can limit NO synthesis. Poly-L-arginine inhibits L-arginine uptake more effectively than other cationic proteins and exerts additional direct inhibitory effects on NO synthesis.
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PMID:Cationic proteins inhibit L-arginine uptake in rat alveolar macrophages and tracheal epithelial cells. Implications for nitric oxide synthesis. 1042 96

Cellular mechanisms of sepsis-induced ileus remain an enigma. The study aim was to determine the role of nitric oxide (NO) in mediating the suppression of rat jejunal circular smooth muscle activity during endotoxemia. Isolated muscularis inducible NO synthase (iNOS) mRNA was measured by RT-PCR, immunohistochemistry was employed to localize iNOS protein, and contractile activity was measured in an organ bath. The low basal expression of muscularis iNOS mRNA expression was increased in a time-dependent fashion after lipopolysaccharide (LPS), resulting in a 20-fold increase over controls 3 h after injection. Immunohistochemistry of muscularis whole mounts and dissociated muscularis cells for iNOS revealed staining only in the muscularis macrophages 12 h after LPS. LPS caused a 68% reduction in spontaneous muscle activity 12 h after injection, which improved by 53% after the in vitro application of the selective iNOS inhibitor L-N(6)-(1-iminoethyl)lysine. Similar results were obtained in C57BL/6 mice but not in iNOS knockout mice. These data demonstrate that macrophage iNOS plays an important role in mediating LPS-induced intestinal circular muscle suppression.
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PMID:LPS-induced muscularis macrophage nitric oxide suppresses rat jejunal circular muscle activity. 1044 63

The permeability of the outer membrane (OM) to hydrophobic probes and its susceptibility to bactericidal cationic peptides were investigated for natural rough Brucella ovis and for mutant rough Brucella abortus strains. The OM of B. ovis displayed an abrupt and faster kinetic profile than rough B. abortus during the uptake of the hydrophobic probe N-phenyl-naphthylamine. B. ovis was more sensitive than rough B. abortus to the action of cationic peptides. Bactenecins 5 and 7 induced morphological alterations on the OMs of both rough Brucella strains. B. ovis lipopolysaccharide (LPS) captured considerably more polymyxin B than LPSs from both rough and smooth B. abortus strains. Polymyxin B, poly-L-lysine, and poly-L-ornithine produced a thick coating on the surfaces of both strains, which was more evident in B. ovis than in rough B. abortus. The distinct functional properties of the OMs of these two rough strains correlate with some structural differences of their OMs and with their different biological behaviors in animals and culture cells.
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PMID:The outer membrane of Brucella ovis shows increased permeability to hydrophobic probes and is more susceptible to cationic peptides than are the outer membranes of mutant rough Brucella abortus strains. 1053 Dec 86

Burkholderia pseudomallei is a gram-negative bacterium that causes the disease known as melioidosis. This pathogen is endemic to Southeast Asia and northern Australia and is particularly problematic in northeastern Thailand. It has been previously reported that B. pseudomallei is resistant to the killing action of cationic antimicrobial peptides, including human neutrophil peptide, protamine sulfate, poly-L-lysine, magainins, and polymyxins. Recently, we have also found that the virulent clinical isolate B. pseudomallei 1026b is capable of replicating in media containing polymyxin B at concentrations of >100 mg/ml. In order to identify genetic loci that are associated with this particular resistance phenotype, we employed a Tn5-OT182 mutagenesis system in coordination with a replica plating screen to isolate polymyxin B-susceptible mutants. Of the 17,000 Tn5-OT182 mutants screened via this approach, five polymyxin B-susceptible mutants were obtained. Three of these mutants harbored Tn5-OT182 insertions within a genetic locus demonstrating strong homology to the lytB gene present in other gram-negative bacteria. Of the remaining two mutants, one contained a transposon insertion in a locus involved in lipopolysaccharide core biosynthesis (waaF), while the other contained an insertion in an open reading frame homologous to UDP-glucose dehydrogenase genes. Isogenic mutants were also constructed via allelic exchange and used in complementation analysis studies to further characterize the relative importance of each of the various genetic loci with respect to the polymyxin B resistance phenotype exhibited by B. pseudomallei 1026b.
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PMID:Isolation of polymyxin B-susceptible mutants of Burkholderia pseudomallei and molecular characterization of genetic loci involved in polymyxin B resistance. 1054 42

Interleukin-12 (IL-12) plays a pivotal role in the development of T-helper type 1 (Th1) immune response, which may be involved in the pathogenesis of chronic inflammatory autoimmune disorders. In this study, we investigated the effects of N-alpha-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK), serine protease inhibitors, on the production of IL-12 from macrophages stimulated with lipopolysaccharide (LPS). TPCK and TLCK potently inhibited this LPS-induced IL-12 production in a dose-dependent manner. The effect of TPCK and TLCK on the IL-12 p40 promoter activation was analyzed by transfecting monocytic RAW264.7 cells with p40 promoter-reporter constructs. The repressive effect maps to a region in the p40 promoter containing a binding site for NFkappaB (p40-kappaB). A linker scan mutant of the p40-kappaB site abrogates the inhibitory effect on the p40 promoter, confirming the functional relevance of the NFkappaB site. Our results show that TPCK and TLCK inhibit NFkappaB-mediated IL-12 production in macrophages. reserved.
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PMID:Chloromethyl ketones inhibit interleukin-12 production in mouse macrophages stimulated with lipopolysaccharide. 1056 3

P11 cells, derived from the transplantahle rat pituitary tumor 7315a, have been used previously ias a model system to study the regulation of serotonin2A (5-HT2A) receptor expression. As our laboratory has been interested in characterizing the interactions between the 5-HT2A receptor and inducible nitric oxide synthase (iNOS), we have analyzed the Pl I cell line for iNOS expression. Treatment of P ll cells with interferon-gamma and lipopolysaccharide resulted in a 23-fold increase in nitrite production and induced expression of iNOS protein. The increase in nitrite levels was attenuated by the non-selective nitric oxide synthase (NOS) inhibitor N i-nitro-L-arginine methyl ester, hut not the neuronal NOS inhibitor 7-nitroindazole. Typically, Pl 11 cells have been grown in either charcoal-stripped or dialyzed serum-containing medium. We have observed that Pl 1 cells grown under these culture conditions express basal iNOS activity, as evidenced by a 5-fold increase in nitrite accumulation over a 48-hr period, compared with that in cells grown in non-modified serum, which was inhibited by the selective iNOS inhibitor L.N6-(1-iminoethyl)-lysine. Conditioned medium from Pll cells was ahle to stimulate nitrite accumulation in C6 glioma cells, suggesting that the Pl I cells may produce a pro-inflammatory-like factor. As pro-inflammatory cytokines have been shown to modify hormone secretion from the anterior pituitary, the P11 cell line may be a useful in vitro model by which to characterize the function of cells from this organ. In addition, our data suggest that alteration of the microenvironment of the anterior pituitary may result in iNOS expression, possibly altering the function of the hypothalamic-pituitary-adrenal axis.
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PMID:Inducible nitric oxide synthase in P11 cells: expression in the presence of interferon-gamma, lipopolysaccharide, and modified serum. 1066 Jan 17

Our previous report demonstrates that severe gastric mucosal damage is produced in lipopolysaccharide (LPS)-intoxicated rats. In the present study, we examined protective effects of several amino acids including taurine, phenylalanine and L-Arginine on gastric hemorrhagic erosions in acid-irrigated stomachs of LPS rats. The animals were deprived of food for 24 hr. Intravenous LPS (3 mg/kg) was challenged 12 hr after withdrawal of food. Gastric vagotomy was performed, followed by irrigation the stomachs for 3 hr with a physiological acid solution containing 100 mM HCl and 54 mM NaCl. The ulcerogenic parameters including increased gastric acid back-diffusion, mucosal histamine concentrations, lipid peroxide productions, luminal hemoglobin contents, stomach erosions and the lowered glutathione levels were markedly enhanced in LPS rat stomachs irrigated with acid solution. Both phenylalanine and taurine caused dose-dependent attenuations of these ulcerogenic parameters in LPS rats. L-arginine also was effective in inhibition. The inhibitory effect was restored by pretreatment of nitric oxide synthase inhibitors, such as N(G)-nitro-L-arginine-methyl ester or L-N(G)-(1-iminoethyl)-lysine. Furthermore, marked amelioration of hemorrhagic erosions in LPS rats was observed when a combination of these amino acid nutrients was used. The results provide evidence that these amino acid nutrients may ameliorate gastric hemorrhagic erosion via GSH synthesis stimulation, histamine cell membrane stabilization and antioxidant actions in LPS rat stomachs.
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PMID:Protective effects of several amino acid-nutrients on gastric hemorrhagic erosions in acid-irrigated stomachs of septic rats. 1070 90

Previous studies have focused on the immunohistochemical detection of a nitric oxide (NO)-cyclic 3',5'-monophosphate (cGMP) pathway in the brain and pituitary of the aquatic toad Xenopus laevis. We here investigate the endogenous production and possible involvement of NO signaling in the regulation of melanotrope cell activity in the pituitary pars intermedia of this amphibian. Using immunohistochemical staining of cultured cells with a polyclonal antiserum against inducible NO synthase (iNOS), immunoreactivity was observed both in melanotropes and in stellate-shaped cells. Part of these stellate-shaped cells is characterized as folliculo-stellate cells by their capacity of beta-Ala-Lys-N(epsilon)-AMCA uptake. Using chemiluminescence detection we demonstrate the presence of NO and reaction products like nitrite (NO(-)(2)) or peroxynitrite (ONOO(-)) in the incubation medium of cultured melanotropes. Bacterial lipopolysaccharide (LPS) stimulates the generation of NO and reaction products, the effect of which was blocked by S-methyl-l-thiocitrulline hydrochloride, a potent general NOS inhibitor. With [(3)H]lysine incorporation and a superfusion technique, it is shown that peptide release from melanotropes is stimulated by administration of superoxide dismutase (SOD), which was added to the superfusion medium to prevent scavenging of NO by superoxide anions. Pretreating the cells with the general NOS inhibitor l-nitroarginine methyl ester for 48 h attenuated the SOD-induced stimulation, but did not affect the stimulation by sodium nitroprusside (SNP) or 3-morpholinylsydnoneimine chloride (SIN-1), whereas hemoglobin blocked the combined effect of SOD plus NO donors. The soluble guanylate cyclase inhibitor 1H-[1,2, 4]oxadiazolo[4,3a]-quinoxaline-1-one did not inhibit but even significantly potentiated the effect of NO donors on peptide release without affecting the SOD-induced stimulation of peptide release. In addition to the previously described neuronal NOS (nNOS) immunoreactivity in nerve fibers in the pars intermedia of Xenopus, the present data reveal iNOS and nNOS as potential sources of endogenous NO production in cultured cells of the pars intermedia. Our study shows that also in nonmammalian vertebrates endogenous NO production may be physiologically relevant under conditions where protection against oxidative damage is needed. The endocrine cells of the pars intermedia themselves, as well as the folliculo-stellate cells, under such conditions may dispose of a protective mechanism against oxidative stress. The sensitivity of the endogenous NO production to LPS suggests that NO may also play a role during systemic inflammation.
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PMID:Endogenous production of nitric oxide and effects of nitric oxide and superoxide on melanotrope functioning in the pituitary pars intermedia of Xenopus laevis. 1073 69

Blockade or gene deletion of inducible nitric oxide synthase (iNOS) fails to fully abrogate all the sequelae leading to the high morbidity of septicemia. An increase in substrate uptake may be necessary for the increased production of nitric oxide (NO), but arginine is also a precursor for other bioactive products. Herein, we demonstrate an increase in alternate arginine products via arginine and ornithine decarboxylase in rats given lipopolysaccharide (LPS). The expression of iNOS mRNA in renal tissue was evident 60 but not 30 min post-LPS, yet a rapid decrease in blood pressure was obtained within 30 min that was completely inhibited by selective iNOS blockade. Plasma levels of arginine and ornithine decreased by at least 30% within 60 min of LPS administration, an effect not inhibited by the iNOS blocker L-N(6)(1-iminoethyl)lysine (L-NIL). Significant increases in plasma nitrates and citrulline occurred only 3-4 h post-LPS, an effect blocked by L-NIL pretreatment. The intracellular composition of organs harvested 6 h post-LPS reflected tissue-specific profiles of arginine and related metabolites. Tissue arginine concentration, normally an order of magnitude higher than in plasma, did not decrease after LPS. Pretreatment with L-NIL had a significant impact on the disposition of tissue arginine that was organ specific. These data demonstrate changes in arginine metabolism before and after de novo iNOS activity. Selective blockade of iNOS did not prevent uptake and can deregulate the production of other bioactive arginine metabolites.
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PMID:Bioactive products of arginine in sepsis: tissue and plasma composition after LPS and iNOS blockade. 1083 47

Osteopontin has been shown to inhibit the induction of inducible nitric oxide synthase (iNOS, or NOS2) by lipopolysaccharide and interferon-gamma in the RAW264.7 mouse monocyte/macrophage line and in primary mouse proximal tubule epithelial cells. However, the RAW264.7 cells become refractory to the action of OPN after several subcultures or under dilute culture conditions, possibly because of changes in the composition of the extracellular matrix. We make this suggestion because if the cells are plated on a collagen type I or collagen type IV substrate the inhibitory action of OPN is completely suppressed; this is not the case on substrates consisting of laminin, fibronectin, poly-D-lysine, or poly-(2-hydroxyethylmethylacrylate). These observations imply that macrophages are sensitive to regulation by OPN only in certain physiological contexts. Both hyaluronate, which binds CD44, and rat IgGs are also able to inhibit the induction of NO synthesis by the inflammatory mediators. The similar actions of HA and OPN are consistent with the possibility that CD44 may be a receptor for OPN.
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PMID:Regulation of no synthesis induced by inflammatory mediators in RAW264.7 cells: collagen prevents inhibition by osteopontin. 1085 58


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