Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) that are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO(.), a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels and a decrease in ferritin synthesis. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO(+) (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels and a dramatic increase in ferritin synthesis. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels and an increase in ferritin synthesis in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO(+)-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.
 ...
PMID:Nitric oxide-mediated modulation of iron regulatory proteins: implication for cellular iron homeostasis. 1254 30

Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) which are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO*, a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO+ (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO+-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.
 ...
PMID:Role of nitric oxide in cellular iron metabolism. 1257 72

In this study we have analyzed bacterial lipopolysaccharide (LPS) induced genes in hemocytes of the Lepidopteran species Galleria mellonella using subtractive hybridization, followed by suppressive PCR. We have found genes that show homologies to molecules, such as gloverin, peptidoglycan recognition proteins and transferrin known to be involved in immunomodulation after bacterial infection in other species. In addition, a few molecules previously not described in the innate immune reactions were detected, such as a RNA binding molecule and tyrosine hydroxylase. Furthermore, the full-length cDNA of a LPS-induced molecule with six toxin-2-like domains is described to be a promising candidate to further elucidate the relationship between toxin- and defensin-like domains in arthropod host defense.
 ...
PMID:Identification of immunorelevant genes from greater wax moth (Galleria mellonella) by a subtractive hybridization approach. 1259 Sep 72

Both desferrioxamine (DFO) and chloroquine can significantly reduce hepatic iron in experimental animals with iron overload by chelating iron from the low-molecular-weight pool or decreasing iron uptake by the transferrin-transferrin receptor cycle, respectively. However, no previous studies have investigated whether combination therapy of these two drugs would further decrease the tissue iron overload as well as iron-induced toxicity. Chloroquine administration, 15 mg/kg, 5x/week, to rats during the iron loading regime, 10 mg/kg, 3x/week for 4 weeks, significantly decreased both hepatic (54%) and macrophage iron content (24%). However when administered in combination with desferrioxamine, 10 mg/kg, 3x/week for 2 weeks at the cessation of iron loading, no further reduction of hepatic iron content was noted while the iron content of the macrophages significantly increased, possibly indicating the flux of ferrioxamine through these cells. Further studies are warranted to investigate the speciation of iron within these macrophages. Macrophages isolated from chloroquine-treated iron loaded rats showed a reduction in latent NFkappaB activation and a significant increase in lipopolysaccharide-stimulated nitrite release by comparison to these parameters in iron loaded macrophages. Co-administration of chloroquine and desferrioxamine normalised the latent activity of NFkappaB to that of control macrophages as well as increasing LPS-stimulated NO release towards control values. However, DFO alone did not have any significant effect upon either of these parameters. Such results may have important relevance for the reduced immune function of iron loaded macrophages isolated from thalassaemia patients receiving chelation therapy and their propensity to increased infection.
 ...
PMID:Changes in function of iron-loaded alveolar macrophages after in vivo administration of desferrioxamine and/or chloroquine. 1262 Jun 71

We have previously demonstrated that a non-cytokine serum protein called transferrin was a primary activating molecule of the goldfish (Carassius auratus) macrophage antimicrobial response. The ability of the enzymatically cleaved forms of this protein to modulate fish macrophage function is novel and may represent a primitive and evolutionary conserved mechanism for the induction of NO response of macrophages. In the present study we confirm our earlier findings using immunoaffinity purified goldfish transferrin from mitogen-stimulated leukocyte supernatants. In addition we demonstrate that: (1). products released by necrotic/damaged cells contain transferrin-cleaving activity; (2). the cleavage site is located within the bridge peptide connecting the two lobes of the transferrin molecule; (3). transferrin is expressed by activated goldfish macrophages but not mitogen-stimulated kidney leukocytes; and (4). addition of transferrin significantly enhanced the killing response of goldfish macrophages exposed to different pathogens or pathogen products (e.g. lipopolysaccharide, Mycobacterium chelonei, Trypanosoma danilewskyi, Aeromonas salmonicida, and Leishmania major). We propose a model of fish macrophage activation that is mediated by a non-cytokine host protein (i.e. transferrin) in combination with highly conserved innate immunity recognition receptors that are almost certain to exist in teleost.
 ...
PMID:Transferrin and the innate immune response of fish: identification of a novel mechanism of macrophage activation. 1269 11

The iron regulatory proteins (IRPs) are an example of different proteins regulating the same metabolic process, iron uptake and metabolism. IRP1 is an iron-sulfur cluster-containing protein that can be converted from a cytosolic aconitase to an RNA binding posttranscriptional regulator in response to nitric oxide (NO). IRP2 lacks aconitase activity and its expression is decreased by NO signaling. In macrophages, NO is produced in response to such inflammatory ligands as interferon-gamma, which is expressed in response to mitogenic and antigenic stimuli, and lipopolysaccharide, a marker of bacterial invasion. Until recently, research results predict that the cellular response to increased NO production should be a decrease in ferritin synthesis, due to IRP1 binding to ferritin mRNA, and an increase in transferrin receptor biosynthesis, due to IRP1 binding to the transferrin mRNA. Surprisingly, however, macrophages exhibit decreased transferrin receptor concentration in response to inflammatory ligands. Bouton and Drapier discuss the physiological role and the mechanisms that may underlie this contradictory response.
 ...
PMID:Iron regulatory proteins as NO signal transducers. 1274 46

Acute respiratory distress syndrome (ARDS) is associated with altered plasma and lung iron chemistry. Iron can promote microbial virulence and catalyse pro-oxidant reactions, thereby contributing to the oxidative stress that characterises the syndrome. Therefore, the expression of ferritin and transferrin receptors (TfR) were sought in the lungs and hearts of rodents treated with lipopolysaccharide (LPS), and measurements of TfR and ferritin protein expression were taken from lung biopsy specimens from patients with ARDS and appropriate controls. TfR messenger ribonucleic acid (mRNA) was significantly upregulated in the lungs and significantly downregulated in the hearts of rats 4 h after LPS. Ferritin mRNA levels (light and heavy chains) remained unaltered. Protein TfR levels were significantly upregulated in lungs and downregulated in hearts 4 h post-LPS. Ferritin protein levels were significantly downregulated in lungs compared to baseline values but were unaltered in hearts. Nonhaem iron levels were increased in lungs and decreased in hearts, and iron-regulatory-protein activity increased in hearts but not lungs. TfR protein levels were significantly increased in lung biopsies from patients with ARDS compared to controls. Transferrin receptors are upregulated in rodent lungs during inflammation but are downregulated in the heart. Transferrin receptor protein levels were significantly increased in the lungs in clinical acute respiratory distress syndrome. These findings have implications for the pathogenesis of acute respiratory distress syndrome, especially in relation to the role of iron as a mediator of oxidative stress.
 ...
PMID:Variable tissue expression of transferrin receptors: relevance to acute respiratory distress syndrome. 1295 70

The immunogenic antigens of Vibrio vulnificus serovar E were investigated in the eel. Fish were vaccinated by immersion with Vulnivaccine (V), revaccinated 2 years later by intraperitoneal injection (RV) and bath infected 15 days post-revaccination (RVI). The specific immune response in serum was followed in all groups, and selected sera were used for immunostaining of surface (SA) and extracellular antigens (ECA). Bacteria were grown in iron-rich (TSB and MSWYE) and iron-poor media (TSB and MSWYE plus human transferrin (TSB-T and MSWYE-T)) as well as eel serum (ES), and their SA and ECA were extracted and electrophoretically analysed. Cells grown in MSWYE-T and ES presented the same antigenic profiles, which suggests that iron-restriction is the main growth-limiting factor in vivo. The electrophoretic pattern of SA, but not that of ECA, varied with iron-availability in the growth medium. Further, SA extracted from bacteria grown in iron restriction were strongly immunogenic for eels, especially after vaccination and infection. Among the immunogenic antigens over expressed in iron-restriction, three outer membrane proteins of around 70-80 kDa, including the putative receptor for vulnibactin, together with the rapid and slow migrating forms of the lipopolysaccharide (LPS), were identified. The response was not so evident in the case of capsule, which was not clearly stained with any of the eel sera. With respect to ECA, two proteins, identified as the V. vulnificus protease (Vvp) and the major outer membrane protein (OMP), probably liberated to the medium after cell death, were recognised by RV and, more strongly, by RVI sera. The specific antibodies against the mentioned OMPs, LPS bands and the Vvp may contribute to the protection of vaccinated eels against infection, giving a reasonable explanation for the high effectiveness of Vulnivaccine.
 ...
PMID:Immunogenic antigens of the eel pathogen Vibrio vulnificus serovar E. 1527 7

Bovine and possum macrophages were infected in vitro with a virulent strain of Mycobacterium bovis, and mycobacterial replication was measured in the infected macrophages cultured under a variety of conditions. Virulent M. bovis replicated substantially in alveolar possum macrophages as well as in bovine blood monocyte-derived macrophages. Addition of recombinant bovine interferon-gamma (IFN-gamma) with low concentrations of lipopolysaccharide (LPS) rendered bovine macrophages significantly more resistant to M. bovis replication. Disruption of iron levels in infected macrophages by addition of apotransferrin or bovine lactoferrin blocked replication of M. bovis in both bovine and possum macrophages. On the other hand, addition of exogenous iron, either in the form of iron citrate or iron-saturated transferrin, rendered macrophages of both species much more permissive for the replication of M. bovis. The impact of iron deprivation/loading on the mycobacteriostatic activity of cells was independent of nitric-oxide release, as well as independent of the generation of oxygen radical species in both possum and bovine macrophages. Exogenous iron was shown to reverse the ability of IFN-gamma/LPS pulsed bovine macrophages to restrict M. bovis replication. When autologous possum lymphocytes from animals vaccinated with M. bovis strain BCG were added to infected macrophages, they rendered the macrophages less permissive for virulent M. bovis replication. Loading the cells with iron prior to this macrophage-lymphocyte interaction, reversed this immune effect induced by sensitized cells. We conclude that, in two important animal species, intracellular iron level plays an important role in M. bovis replication in macrophages, irrespective of their activation status.
 ...
PMID:Iron modulates the replication of virulent Mycobacterium bovis in resting and activated bovine and possum macrophages. 1599 92

Few acute phase proteins are known in fish and better knowledge of them would provide a basis for more reliable methods to objectively assess fish health and welfare. An acute phase response was induced in rainbow trout (Oncorhynchus mykiss, Walbaum) by inflammation triggered by intraperitoneal administration of purified Aeromonas salmonicida lipopolysaccharide emulsified in Freund's incomplete adjuvant (LPS/FIA) or a commercial oil-based multivalent vaccine. Acute phase proteins were characterized by comparative densitometry of plasma proteins separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and identified by MALDI-TOF and ESI MS/MS mass spectrometry. In one experiment, plasma samples were compared between treatment and control groups in which fish were terminally bled. In another experiment, individual fish were sampled repeatedly. Proteins scored as increased were those whose normalized value increased three-fold or greater between pre- and post-stimulus. Proteins scored as decreased were those whose normalized values decreased two-fold or greater. Unaltered proteins were those that were not altered or did not meet either of these criteria. Proteins that were absent in pre-stimulus gels but present in post-stimulus profiles were considered to be induced. Only those proteins that were altered in all fish for a given treatment were considered. In both experiments, protein p36 was increased up to 13-fold and several proteins were detected that had not been previously. In all fish treated with LPS/FIA, p9.5 was consistently increased an average of 75-fold in plasma. We have constructed a plasma protein panel of eight increased or induced proteins (p9.5, p10.5, p24a, p24b, p24c, p25a, p36 and p37), one decreased (p16) and two that are unaltered (p28a, p28b) in rainbow trout following inflammation or injection with LPS/FIA. Proteins from this panel that were similar to previously identified proteins were pre-cerebellin-like (p24a), transferrin (p37) and apolipoprotein (p10.5, p24c and p28).
 ...
PMID:Plasma proteomic analysis of the acute phase response of rainbow trout (Oncorhynchus mykiss) to intraperitoneal inflammation and LPS injection. 1613 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>