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)

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an attenuation of hemodynamic alterations and an altered pattern of inflammatory mediator release. Therefore, we measured main hemodynamic variables such as systemic and pulmonary artery pressure, cardiac output, heart rate, central venous pressure, and pulmonary artery wedge pressure, as well as the time-course of thromboxane-B2, 6-keto-PGF1 alpha, and interleukin 6 formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Circ Shock 35:237-244, 1991). Induction of the stress response was carried out by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenaspartate) = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 (HSP70) expression in the lungs, liver, and kidneys and significantly increased plasma levels of interleukin 6, 6-keto-PGF1 alpha, and thromboxane-B2, compared with untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators compared with the untreated group. Hemodynamic data presented significantly decreased peak pulmonary artery pressure and pulmonary vascular resistance index values, significantly increased systemic artery pressure and systemic vascular resistance index values, and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of HSP70 by Zn2+ attenuates the liberation of inflammatory mediators, as well as the course of hemodynamic variables due to LPS.
 ...
PMID:The influence of heat shock protein 70 induction on hemodynamic variables in a porcine model of recurrent endotoxemia. 916 71

The expression of heat shock proteins (HSPs) as stress-induced proteins was studied in mice injected with D-galactosamine (D-GalN) and lipopolysaccharide (LPS) as an experimental endotoxic shock model. The expression of constitutive type heat shock protein 70 (HSC70) was significantly reduced in livers of mice injected with D-galactosamine and lipopolysaccharide, while its expression was unaffected in livers of mice injected with D-galactosamine or lipopolysaccharide alone. The expression of other constitutive type heat shock proteins, namely HSP60, HSP32 and HSP25 was also reduced in mice injected with D-galactosamine and lipopolysaccharide. On the other hand, inducible type HSP70 was detected in livers from mice injected with D-galactosamine and lipopolysaccharide, but not in livers from mice injected with D-galactosamine or lipopolysaccharide alone. Simultaneous injection of anti-tumor necrosis factor (TNF)-alpha antibody prevented the liver from reduced expression of constitutive type HSC70, and lead to marked expression of inducible type HSP70 in the liver. Reduced expression of constitutive type HSC70 was also found when D-galactosamine and recombinant TNF-alpha was injected. Therefore, TNF-alpha was suggested to play a critical role on altered expression of constitutive HSC70 and inducible type HSP70 in response of D-galactosamine-sensitized mice to lipopolysaccharide.
 ...
PMID:Altered expression of constitutive type and inducible type heat shock proteins in response of D-galactosamine-sensitized mice to lipopolysaccharide as an experimental endotoxic shock model. 965 19

Glial activation and oxidative stress are both consequences of brain aging. To investigate whether glial activation causes oxidative stress or not, the immune activator, lipopolysaccharide (LPS), was intraventricularly injected into the rat brain. The expression of candidate genes were examined by in situ hybridization histochemistry (ISHH) combined with immunohistochemistry for glial markers over a period of time up to 24 h after the LPS injection. The mRNA for glial fibrillary acidic protein (GFAP) was elevated around the injection site by 2 h, and the volume of elevated expression spread to the entire brain after 6 h, with higher levels present in the injected hemisphere. The level of inducible isoform of nitric oxide synthase (i-NOS) mRNA increased in a punctate-like pattern in the region of the injection by 6 h and this response spread to the entire brain after 12 h. These results indicate that the glia are activated for at least 24 h after a single LPS injection. The mRNAs for a heat-shock protein (HSP70) and for the manganese-dependent superoxide dismutase (Mn-SOD) were elevated in the ipsilateral hemisphere as early as 2 h post-injection, but these responses subsided nearly to basal levels by 4 h. These levels of mRNAs for these genes increased again after 6 h of the LPS injection; thus, the earlier increases of the messages appeared to be associated with the survival surgery procedure. With microautoradiographic analysis, scattered OX-42 positive cells expressed i-NOS mRNA after 6 h post-injection, but elevation of Mn-SOD mRNA was not detected in either microglia or astrocytes at any time point examined. The level for Cu/Zn-SOD mRNA did not alter at any time point. The beta-amyloid precursor protein (betaAPP) mRNAs were elevated beginning at 6 h. These results indicate that chronic glial activation leads to a condition of oxidative stress in the brain. The data also suggest that LPS injection could be used to study the effects of chronic glial activation on the survival of neuronal populations that could be at risk from oxidative stress.
 ...
PMID:Indicators of glial activation and brain oxidative stress after intraventricular infusion of endotoxin. 968 67

Rat C6 glioma cells were stably transfected with a human cDNA encoding heat shock protein (HSP)70. Immunostaining revealed the presence of largely cytosolic HSP70 in C6-hsp70 cells, but not in control (vector transfected) C6-pTK cells. Induction of nitric oxide synthase (NOS-2) expression in C6-hsp70 cells, assessed by nitrite accumulation, was significantly reduced compared to control C6-pTK cells (25+/-8% of control cell induction, P < 0.005), when induced with a maximally stimulatory combination of bacterial endotoxin lipopolysaccharide (LPS) plus a mixture of three cytokines ("CM:" TNF-alpha, IL1-beta, and IFN-gamma). Immunostaining for the transcription factor NFkappaB p65 subunit revealed decreased cytokine-dependent nuclear uptake in HSP70 expressing cells compared to control cells. Activation of C6 cell NFkappaB by LPS plus CM required IkappaB degradation by the 20S proteasome, since NOS-2 expression was blocked by a selective proteasome inhibitor. In parental C6 cells, the presence of LPS plus CM caused a rapid (within 30 min) decrease in inhibitory IkappaB-alpha protein levels, and this loss was abolished by prior heat shock of the cells. In contrast, IkappaB-alpha levels in transfected cells were not modified by the expression of HSP70. These results demonstrate that constitutive HSP70 expression in glial cells can reduce NOS-2 induction, presumably due to inhibition of NFkappaB nuclear uptake. Furthermore, whereas prevention of decreases in IkappaB-alpha can account for the suppressive effects of heat shock, the results suggest that HSP70 blocks NOS-2 induction by interfering at a later step in the NFkappaB activation pathway.
 ...
PMID:Suppression of glial nitric oxide synthase induction by heat shock: effects on proteolytic degradation of IkappaB-alpha. 970 Oct 55

Recent studies have shown that the non-steroidal anti-inflammatory drugs (NSAIDs) activate heat shock transcription factor (HSF1) from a latent cytoplasmic form to a nuclear, DNA binding state. As HSF1 can function as both an activator of heat shock genes and a repressor of non-heat shock genes such as IL1B and c- fos, we have examined the potential role of HSF1 in the effects of NSAIDs on gene expression in a human monocytic cell line THP-1. We found that two members of the NSAIDs, sodium salicylate and sulindac repress the IL1B promoter to similar degree to heat shock or HSF1 overexpression. In addition, sodium salicylate and additional NSAIDs used at concentrations that activate HSF1 also inhibited the expression of other monocytic genes (TNF-alpha, IL-1beta, IL-6, IL-8, IL-10, ICAM-1) activated by exposure to a pro-inflammatory stimulus (lipopolysaccharide, LPS). At least in the case of the IL1B promoter, repression did not seem to involve another factor whose activity is affected by the NSAIDs, NFkappaB as the IL1B promoter fragment used in our studies is not NFkappaB responsive and binds specifically to HSF1. Exposure to NSAIDs had a complex effect on HSP gene expression and while sulindac activated the stress responsive HSP70B promoter, sodium salicylate did not. In addition, only a subset of the NSAIDs induced HSP70 mRNA species. These findings reflect the properties of HSF1 which can be activated to at least two DNA binding forms only one of which activates heat shock promoters and suggest that individual NSAID family members may differentially induce one or other of these forms. Overall therefore, exposure to NSAIDs leads to a profound switch in gene expression in monocytic cells, with suppression of genes involved in macrophage activation and induction of stress genes and HSF1 appears to play a regulatory role in these effects.
 ...
PMID:Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes. 1032 74

Stress response is mediated by a number of stress-related gene products and is crucial for maintenance of homeostasis during and after various cellular stresses. Exposure of rats to restraint and water-immersion stress rapidly and transiently activated heart shock factor 1 (HSF1) and caused rapid HSP70 mRNA expression and HSP70 accumulation in gastric mucosa. Using protein-malnourished, bilateral adrenalectomized, and subdiaphragmatically vagotomized rats, we showed that this heat shock response was regulated by the hypothalamic-pituitary-adrenocortical or the sympathoadrenal systems. Experiments with inhibitors for adrenoceptor subtypes and glucocorticoids suggested that the alpha 1A-adrenergic receptor appeared to mediate the HSP70 induction. The extent of HSP70 induction inversely correlated to the severity of mucosal damage, suggesting an important role of the heat shock response in gastric mucosal defense under conditions of stress. Recently, we found that gastric surface mucous cells possessed a phagocyte NADPH oxidase-like system and secreted abundant superoxide anion (O2.-). Helicobactor pylori lipopolysaccharide markedly up-regulated this secretion. The enhanced O2.- production activated nuclear factor kappa B by autocrine/paracrine mechanisms, resulting in activation of proinflammatory cytokine gene expressions. These results suggest that surface mucous cells may actively regulate stress responses of Helicobacter pylori-infected gastric mucosa through a phagocyte NADPH oxidase-like activity.
 ...
PMID:[Molecular stress response in the stomach]. 1062 39

Expression of inflammatory nitric oxide synthase (NOS2) is mediated by transcription factor NFkappaB. By using the specific proteasome inhibitor lactacystin to examine IkappaB degradation, we observed a paradoxical increase in lipopolysaccharide- and cytokine-dependent NOS2 expression at low concentrations or when lactacystin was added subsequent to cytokines. Lactacystin reduced the initial accumulation of NOS2 mRNA but reduced its subsequent decrease. Lactacystin increased NOS2 promoter activation after 24 h, but not after 4 h, and similarly prevented initial NFkappaB activation and at later times caused NFkappaB reactivation. Lactacystin reduced initial degradation of IkappaB-alpha and IkappaB-beta, however, at later times selectively increased IkappaB-beta, which was predominantly non-phosphorylated. Expression of full-length rat IkappaB-beta, but not a carboxyl-terminal truncated form, inhibited NOS2 induction and potentiation by lactacystin. Lactacystin increased IkappaB-beta expression in the absence of NOS2 inducers, as well as expression of heat shock protein 70, and the heat shock response due to hyperthermia increased IkappaB-beta expression. These results suggest that IkappaB-beta contributes to persistent NFkappaB activation and NOS2 expression in glial cells, that IkappaB-beta is a stress protein inducible by hyperthermia or proteasome inhibitors, and that delayed addition of proteasome inhibitors can have stimulatory rather than inhibitory actions.
 ...
PMID:Inhibitory and stimulatory effects of lactacystin on expression of nitric oxide synthase type 2 in brain glial cells. The role of Ikappa B-beta. 1082 92

We examined gene expression of heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), which is the rate limiting enzyme in heme catabolism and is also known as heat shock protein 32 (HSP32), in the rat brain using a sepsis model induced by bacterial lipopolysaccharide (LPS). Intraperitoneal injection of LPS (10 mg/kg) to rats caused the elevation of body temperature and white blood cell (WBC) counts as well as marked elevation of serum interleukin-6 (IL-6) level, showing the typical pathological characteristics of sepsis. In this model, HO-1 mRNA increased at 6 h after LPS administration and continued to rise until 30 h. In contrast, HSP70 mRNA increased only between 3 h and 6 h after LPS administration, returning completely to the control level by 12 h. HO-1 mRNA was expressed predominantly in the cortex and the medulla oblongata, while HSP70 mRNA was expressed mainly in the striatum. HO-1 and HSP70 mRNA levels thus showed distinctive time courses and tissue distribution in the brain, suggesting that gene expression of these heat shock proteins (HSPs) is separately regulated.
 ...
PMID:Differential induction of brain heme oxygenase-1 and heat shock protein 70 mRNA in sepsis. 1085 Mar 69

In this study, the anti-inflammatory actions of the peroxisome proliferator-activated receptor (PPAR)-gamma agonists 15-deoxy-delta 12,14-prostaglandin J2 (15-d-delta 12,14-PGJ2) and troglitazone have been examined. Treatment of RAW 264.7 cells and CD-1 mouse peritoneal macrophages with lipopolysaccharide (LPS) + interferon-gamma (IFN-gamma) results in inducible nitric oxide synthase (iNOS), inducible cyclooxygenase (COX-2) and interleukin-1 (IL-1) expression, increased production of nitric oxide, and the release of IL-1. In a concentration-dependent manner, 15-d-delta 12,14-PGJ2 inhibits each of these proinflammatory actions of LPS + IFN-gamma, with half-maximal inhibition at approximately 0.5 microg/ml and complete inhibition at 1-5 microg/ml. The inhibitory actions of 15-d-delta 12,14-PGJ2 on LPS + IFN-gamma-induced inflammatory events are not associated with the inhibition of iNOS enzymatic activity or macrophage cell death, but appear to result from an inhibition of iNOS and IL-1 transcription. In addition, the anti-inflammatory actions of 15-d-delta 12,14-PGJ2 are not limited to peritoneal macrophages, as 15-d-delta 12,14-PGJ2 prevents TNF-alpha + LPS-induced resident islet macrophage expression of IL-1beta and beta-cell expression of iNOS stimulated by the local release of IL-1 in rat islets. 15-d-delta 12,14-PGJ2 appears to be approximately 10-fold more effective at inhibiting resident islet macrophage activation (in response to TNF + LPS) than IL-1-induced nitrite production by beta-cells. Two mechanisms appear to be associated with the antiinflammatory actions of both 15-d-delta 12,14-PGJ2 and troglitazone: 1) the direct inhibition of cytokine- and endotoxin-stimulated iNOS and IL-1 transcription; and 2) the inhibition of IL-1 signaling, an event associated with PPAR-gamma agonist-induced activation of the heat shock response (as assayed by heat shock protein 70 expression). These findings indicate that the PPAR-gamma agonists, troglitazone and the J series of prostaglandins, are potent anti-inflammatory agents that prevent cytokine- and endotoxin-stimulated activation of peripheral and resident tissue macrophages and cytokine-induced iNOS expression by beta-cells by the inhibition of transcriptional activation and induction of the heat shock response.
 ...
PMID:Anti-inflammatory actions of 15-deoxy-delta 12,14-prostaglandin J2 and troglitazone: evidence for heat shock-dependent and -independent inhibition of cytokine-induced inducible nitric oxide synthase expression. 1086 55

To improve the reliability of the serodiagnosis of Chlamydia trachomatis infections, an immunoblot analysis, a microimmunofluorescence titration, and different immunoassays using synthetic peptides derived from species-specific epitopes in variable domain IV of the major outer membrane protein or recombinant antigens (heat shock protein 70 [hsp70], hsp60, hsp10, polypeptide encoded by open reading frame 3 of the plasmid [pgp3], macrophage infectivity potentiator, and a fragment of the total lipopolysaccharide) were evaluated. Because cross-reactions between chlamydial species have been reported, the microimmunofluorescence tests were also performed with Chlamydia pneumoniae and Chlamydia psittaci used as antigens, and C. pneumoniae-specific antibodies were also determined by immunoassays. Since the presence of antimicrobial antibodies must be interpreted in light of their prevalence in the general population, responses obtained with serum samples from patients with well-defined infection (i.e., with positive urethral or endocervical C. trachomatis DNA amplification) were compared to those obtained with samples from healthy blood donors. The best sensitivity (86%) with a specificity of 81% was obtained for immunoblotting results, when the number of individuals with > or =10 immunoglobulin G (IgG) and/or > or =2 IgM responses to the different C. trachomatis antigens was considered. A 13-kDa antigen was recognized by most of the samples (86% for IgG) from patients with acute urogenital infection but rarely (3%) by those from healthy blood donors (P < 0.0001). The sensitivity and specificity results obtained for serum antibodies to peptides or recombinant antigens were slightly lower than those results obtained for the number of responses to whole C. trachomatis antigens, which were 76 and 77%, respectively, when IgG responses to both recombinant hsp60 and pgp3 were considered.
 ...
PMID:Chlamydial serology: comparative diagnostic value of immunoblotting, microimmunofluorescence test, and immunoassays using different recombinant proteins as antigens. 1155 74


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