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 thiol reducing agent N-acetylcysteine (NAC) is commonly used as an "antioxidant" in studies examining gene expression, signaling pathways, and outcome in acute and chronic models of lung injury. It is less widely appreciated that NAC can also undergo auto-oxidation and behave as an oxidant. We showed previously that NAC can have opposite effects on the activation of nuclear factor-kappaB depending on whether or not serum is present, and that the effects of NAC in the absence of serum are mimicked by various oxidants. Here we show that in a serum-depleted environment (0.1% fetal bovine serum), NAC substantially inhibited lipopolysaccharide (LPS) activation of the mitogen-activated protein kinases (MAPKs), namely extracellular signal-regulated kinase (ERK), p38mapk, and c-Jun NH2-terminal kinase (JNK). By contrast, in the presence of 10% serum, NAC had no effect on LPS activation of p42 and p44 ERK and in fact enhanced LPS induction of p38mapk and JNK phosphorylation. Because serum can significantly alter the redox state, these findings highlight the importance of the local redox milieu in signal transduction.
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PMID:Redox paradox: effect of N-acetylcysteine and serum on oxidation reduction-sensitive mitogen-activated protein kinase signaling pathways. 1135 Aug 34

Protease-activated receptor-2 (PAR-2) acts as a modulator of multiple physiological/pathophysiological functions including salivary exocrine secretion. Given the supersensitivity of endothelial PAR-2 under endotoxaemia, we investigated if endotoxin/lipopolysaccharide (LPS) could alter the sensitivity of PAR-2 in the salivary glands. The in vivo salivation in response to i.v. administration of the PAR-2-activating peptide SLIGRL-NH2, but not of carbachol, gradually decreased 6-20 h after LPS administration in the mice. The LPS-induced hyporeactivity to the PAR-2 agonist was partially reversed by repeated administration of aprotinin, a non-specific protease inhibitor. PAR-2 mRNA levels in the salivary glands, as assessed by the semi-quantitative RT-PCR analysis, remained unchanged following LPS challenge. Our findings indicate that in contrast to the supersensitivity of endothelial PAR-2 as described previously, subsensitivity of PAR-2 in the salivary glands develops during the LPS-induced systemic inflammation, which might involve desensitisation of PAR-2 by endogenous proteases.
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PMID:Lipopolysaccharide-induced subsensitivity of protease-activated receptor-2 in the mouse salivary glands in vivo. 1152 Nov 72

The role of the D-isomeric form of the salivary gland tripeptide FEG (feG) and its carboxyl-amidated derivative, feG(NH2), in regulating leukocyte adherence to nonfixed atrial slices from Sprague-Dawley rats was examined under static conditions. Optimal binding of the leukocytes was seen if the leukocytes were treated with platelet activating factor (PAF; 10(-9)M). The increased adherence of PAF-treated peripheral blood leukocytes was totally inhibited by both feG and feG(NH2) (10-9M), as well as by antibodies against CD18 and CD49d. In contrast, the binding of peritoneal leukocytes was blocked only by CD49d antibody. Circulating leukocytes obtained from lipopolysaccharide (LPS) treated (2 mg/kg ip) rats did not bind to atrial slices obtained from normal hearts, but readily bound to atrial slices obtained from LPS-treated rats. This leukocyte binding was inhibited by in vivo feG treatment (100 microg/kg ip, 24 h before harvest) or by treating the isolated cells with feG (10(-9)M). The amidated peptide feG(NH2) reduced neutrophil accumulation in the atrium elicited by ip injection of LPS, whereas feG was ineffective. The reduction in neutrophil infiltration into the myocardium by feG(NH2) and the prevention of leukocyte interaction with myocytes seen with both feG and feG(NH2) probably results in hindered leukocyte migration in the inflamed heart, resulting in less tissue damage. The inhibition by these tripeptides on neutrophil adhesion to myocytes suggests that salivary glands hormones regulate the severity of cardiac inflammation.
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PMID:Regulation of leukocyte adhesion to heart by the tripeptides feG and feG(NH2). 1159 79

The effect of quercetin on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was studied. Quercetin pretreatment significantly inhibited NO production in an LPS-stimulated RAW 264.7 murine macrophage cell line. Post-treatment with quercetin partially inhibited NO production. The inhibitory action of quercetin was due to neither the cytotoxic action nor altered LPS binding. The expression of inducible-type NO synthase (iNOS) was markedly down-regulated by quercetin. Quercetin suppressed the release of free nuclear factor (NF)-kappaB by preventing degradation of IkappaB-alpha and IkappaB-beta. Moreover, quercetin blocked the phosphorylation of extracellular signal regulated kinase 1/2 (Erk 1/2), p38, and c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and, further, the activity of tyrosine kinases in LPS-stimulated RAW cells. Quercetin also inhibited interferon (IFN)-gamma-induced NO production. Taken together, these results indicate that the inhibitory action of quercetin on NO production in LPS- and/or IFN-gamma-stimulated macrophages might be due to abrogation of iNOS protein induction by impairment of a series of intracellular signal pathways.
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PMID:The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells. 1175 12

The endogenous opioid system has been found to be involved in fever caused by pyrogens. Recent work in our laboratory has demonstrated that the mu-opioid receptor is involved in interleukin-1beta (IL-1beta)- and in lipopolysaccharide (LPS)-induced fevers. In the present study, we have investigated the role of the mu-opioid receptor in the preoptic anterior hypothalamus (POAH) in fever induced by interleukin-6 (IL-6). Following stereotaxic implantation of a guide cannula into the POAH for microinjection, radio transmitters to monitor body temperature (Tb) continuously were inserted intraperitoneally. Adult male Sprague-Dawley rats were microinjected with 0.5 microg of the selective mu-opioid receptor antagonist, cyclic D-phe-Cys-Try-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), into the POAH. Thirty min later, IL-6 (100 ng) was injected into the POAH. CTAP significantly blocked the IL-6 fever. CTAP alone had no effect on Tb during the 390-min recording period. These data indicate that mu-opioid receptors within the POAH mediate IL-6 fever and add to the increasing evidence that the opioid system is involved in the pathogenesis of fever in rats.
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PMID:Effect of a mu-opioid receptor-selective antagonist on interleukin-6 fever. 1200 6

Bcl-2 protein family members are among the key regulators of the apoptosis effector phase. Therefore, we investigated the ability of synthetic peptides derived from proteins of the Bcl-2 family, namely, the NH2-terminal region of Bcl-2 (Bcl2_syn), a central domain of Bax (Bax_syn), and a central domain of Bak (Bak_syn) to interfere with the apoptotic process in LLC-PK1 cells. Apoptosis was induced by tacrolimus or lipopolysaccharide treatment, and microinjection of Bcl2_syn into stimulated LLC-PK1 cells significantly reduced the percentage of apoptotic cells detected within 4 h after the treatment. Microinjection of Bax_syn or Bax_syn, in contrast, induced apoptosis in otherwise untreated LLC-PK1 cells during the same period of time. A random sequence control peptide (Control_syn), which served as a negative control, as well as FITC-labeled dextran, which was coinjected in all experiments for visualization, were ineffective in either preventing or inducing apoptosis. These results suggest that synthetic peptides mimicking the functional domains of proteins of the Bcl-2 family are capable of regulating apoptosis when microinjected into LLC-PK1 cells in vivo. Analogs to these regulatory peptides could therefore provide valuable lead compounds in the therapeutical context.
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PMID:Effects of microinjection of synthetic Bcl-2 domain peptides on apoptosis of renal tubular epithelial cells. 1206 Jun 1

Hepatitis C virus (HCV) is remarkably efficient at establishing chronic infection. One of the reasons for this appears to be the suppression of the accessory cell function of professional antigen presenting cells. In the present study, the immunosuppressive activity of HCV protein was examined on dendritic cells (DCs) generated from mouse bone marrow progenitor cells in vitro. We found that the DCs forced to express HCV protein have defective allostimulatory ability. DCs expressing HCV protein were phenotypically indistinguishable from normal DCs. However, they were unable to produce IL-12 effectively when stimulated with lipopolysaccharide. The functional domain of the HCV protein essential for immunosuppression was determined using a series of NH2-and C-terminal deletion mutants of HCV core protein. We found that amino acid residues residing between the 21st and the 40th residues from the NH2-terminus of HCV core protein are required for immunosuppression. These findings suggest that HCV core protein suppresses the elicitation of protective Th1 responses by the inhibition of IL-12 production by DCs.
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PMID:Identification of hepatitis C virus core domain inducing suppression of allostimulatory capacity of dendritic cells. 1213 11

Bacteria-derived synthetic lipoproteins constitute potent macrophage activators in vivo and are effective stimuli, enhancing the immune response especially with respect to low or non-immunogenic compounds. N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)3-lysine (P3CSK4), exhibiting one of the most effective lipopeptide derivatives, represents a highly efficient immunoadjuvant in parenteral, oral, nasal and genetic immunization either in combination with or after covalent linkage to antigen. In order to further elucidate its molecular mode of action with respect to the transcriptional level, we focused our investigations on the P3CSK4-induced modulation of gene transcription. We could show that P3CSK4 activates/represses an array of at least 140 genes partly involved in signal transduction and regulation of the immune response. P3CSK4 activates the expression of tumor suppressor protein p53 (p53), c-rel, inhibitor of nuclear factor kappa B (NFkappaB) alpha (IkappaB alpha), type 2 (inducible) nitric oxide (NO) synthase (iNOS), CD40-LR, intercellular adhesion molecule-1 (ICAM-1) and interleukin 1/6/15 (IL-1/6/15). We detected no activation of heat shock protein (HSP) 27, 60, 84 and 86, osmotic stress protein 94 (Osp 94), IL-12, extracellular signal-regulated protein kinase 1 (ERK1), p38 mitogen activated protein (MAP)-kinase (p38), c-Jun NH2-terminal kinase (JNK), signal transducer and activator of transcription 1 (STAT1), CD14 and caspase genes. Furthermore, we monitored inhibition of STAT6, Janus kinase 3 (Jak3) and cyclin D1/D3 gene transcription after stimulating bone marrow-derived macrophages (BMDM) with lipopeptide. In addition, we monitored significant differences after lipopeptide and lipopolysaccharide (LPS) stimulation of bone marrow-derived murine macrophages. Our findings are of importance for further optimizing both conventional and genetic immunization, and for the development of novel synthetic vaccines.
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PMID:Lipopeptide adjuvants: monitoring and comparison of P3CSK4- and LPS-induced gene transcription. 1234 44

Double-stranded RNA-activated protein kinase (PKR), a serine/threonine kinase, is activated in virus-infected cells and acts as an antiviral machinery of type I interferons. PKR controls several stress response pathways induced by double-stranded RNA, tumor necrosis factor-alpha or lipopolysaccharide, which result in the activation of stress-activated protein kinase/c-Jun NH2-terminal kinase and p38 of the mitogen-activated protein kinase family. Here we showed a novel interaction between PKR and apoptosis signal-regulating kinase 1 (ASK1), one of the members of the mitogen-activated protein kinase kinase kinase family, which is activated in response to a variety of apoptosis-inducing stimuli. PKR and ASK1 showed predominant cytoplasmic localization in COS-1 cells transfected with both cDNAs, and coimmunoprecipitated from the cell extracts. A dominant negative mutant of PKR (PKR-KR) inhibited both the apoptosis and p38 activation induced by ASK1 in vivo. Consistently, PKR-KR inhibited the autophosphorylation of ASK1 in vitro, and exposure to poly(I)-poly(C) increased the phosphorylation of ASK1 in vivo. These results indicate the existence of a link between PKR and ASK1, which modifies downstream MAPK.
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PMID:Double-stranded RNA-activated protein kinase interacts with apoptosis signal-regulating kinase 1. Implications for apoptosis signaling pathways. 1247 8

The authors previously reported increased expression of the Salmonella enterica serovar Typhi (S. typhi) rfaH gene when the bacterial cells reach stationary phase. In this study, using a lacZ fusion to the rfaH promoter region, they demonstrate that growth-dependent regulation of rfaH expression occurs at the level of transcription initiation. It was also observed that production of the lipopolysaccharide (LPS) O-antigen by S. typhi Ty2 correlated with the differential expression of rfaH during bacterial growth. This was probably due to the increased cellular levels of RfaH, since expression of the distal gene in the O-antigen gene cluster of S. typhi Ty2, wbaP, was also increased during stationary growth, as demonstrated by RT-PCR analysis. Examination of the sequences upstream of the rfaH coding region revealed homologies to potential binding sites for the RcsB/RcsA dimer of the RcsC/YopJ/RcsB phosphorelay regulatory system and for the RpoN alternative sigma factor. The expression of the rfaH gene in rpoN and rcsB mutants of S. typhi Ty2 was measured. The results indicate that inactivation of rpoN, but not of rcsB, suppresses the growth-phase-dependent induction of rfaH expression. Furthermore, production of beta-galactosidase mediated by the rfaH-lacZ fusion increased approximately fourfold when bacteria were grown in a nitrogen-limited medium. Nitrogen limitation was also shown to increase the expression of the O-antigen by the wild-type S. typhi Ty2, as demonstrated by a similar electrophoretic profile to that observed during the stationary phase of growth in rich media. It is therefore concluded that the relationship between LPS production and nitrogen limitation parallels the pattern of rfaH regulation under the control of RpoN and is consistent with the idea that RpoN modulates LPS formation via its effect on rfaH gene expression during bacterial growth.
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PMID:O-antigen expression in Salmonella enterica serovar Typhi is regulated by nitrogen availability through RpoN-mediated transcriptional control of the rfaH gene. 1248 Aug 83


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