Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In gallbladder epithelial cells (GBEC), PPARalpha and PPARgamma ligands modulate inflammation by suppression of TNFalpha production and prevent excessive accumulation of cholesterol by ABCA1 activation. Recently, HMG-CoA reductase inhibitors (statins) were shown to activate PPARalpha and PPARgamma in various cells but no studies of their effects in GBEC have been conducted. The objective of this study was, therefore, to determine the effects of statins on PPAR and ABCA1 expression and the anti-inflammatory effect of statins in GBEC. Canine GBEC were cultured on Petri dishes. Expression of the proteins PPARalpha, PPARgamma, and ABCA1 was measured by western blotting analysis after treatment with simvastatin, pravastatin, NO-pravastatin, PPARalpha ligand, or PPARgamma ligand in the culture media. Expression of ABCA1 and LXRalpha mRNAs was estimated by RT-PCR. Expression of TNFalpha mRNA was measured by RT-PCR after 24 h pre-treatment with the statins, preceding 1 h of lipopolysaccharide (LPS) loading. Simvastatin, pravastatin, and NO-pravastatin increased expression of the proteins PPARalpha, PPARgamma, and ABCA1, and expression of the mRNA of ABCA1 and LXRalpha in GBEC. Pre-treatment with simvastatin, pravastatin, and NO-pravastatin suppressed the production of TNFalpha mRNA induced by LPS. In conclusion, statins probably contribute to the preservation of GBEC function by activation of PPARalpha and PPARgamma, which have anti-inflammatory effects by suppression of pro-inflammatory cytokines, and ABCA1 activation mediated by LXRalpha, which prevents the accumulation of cholesterol in GBEC.
...
PMID:HMG-CoA reductase inhibitors (statins) activate expression of PPARalpha/PPARgamma and ABCA1 in cultured gallbladder epithelial cells. 1922 84

The expression of peroxisome proliferator-activated receptor gamma (PPARgamma) was investigated in the hypothalamic-pituitary-adrenal (HPA) axis of weaned pigs after injection with 100 microg/kg bodyweight Escherichia coli lipopolysaccharide (LPS) (n=6) and control pigs injected with sterile saline (n=6). LPS increased PPARgamma mRNA and protein expression in the hypothalamus (23.8 and 3.1-fold relative to controls, respectively), pituitary gland (9.2 and 2.0-fold, respectively) and adrenal gland (3.5 and 2.3-fold, respectively) (P<0.05). LPS also induced an increase in PPARgamma immunohistochemical staining in the hypothalamus (1.3-fold), adenohypophysis (1.3-fold), adrenal cortex (1.4-fold) and adrenal medulla (1.6-fold) (P<0.05). Concurrent with up-regulated expression of PPARgamma, LPS increased the concentrations of plasma corticotrophin-releasing hormone (2.1-fold) and adrenocorticotrophin (1.4-fold) (P<0.05). LPS also induced elevations of interleukin 6 and tumour necrosis factor alpha mRNA levels in the hypothalamus (4.0 and 3.2-fold, respectively), pituitary gland (20.7 and 5.1-fold, respectively) and adrenal gland (3.9 and 3.3-fold, respectively) (P<0.05). PPARgamma may play a role in the regulation of neuroendocrine responses associated with immunological stress in pigs.
...
PMID:Up-regulated expression of peroxisome proliferator-activated receptor gamma in the hypothalamic-pituitary-adrenal axis of weaned pigs after Escherichia coli lipopolysaccharide challenge. 1928 2

The xanthones, alpha- and gamma-mangostin (MG), are major bioactive compounds found in mangosteen and are reported to have antiinflammatory properties in several murine models. Given the association between obesity, chronic low-grade inflammation, and insulin resistance, we examined the effects of alpha- and gamma-MG on markers of inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes treated with lipopolysaccharide (LPS). alpha- and gamma-MG decreased the induction by LPS of inflammatory genes, including tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, monocyte chemoattractant protein-1, and Toll-like receptor-2. Moreover, alpha- and gamma-MG attenuated LPS activation of the mitogen-activated protein kinases (MAPK) c-jun NH(2)-terminal kinase, extracellular signal-related kinase, and p38. alpha- and gamma-MG also attenuated LPS activation of c-Jun and activator protein (AP)-1 activity. gamma-MG was more effective than alpha-MG on an equimolar basis. Furthermore, gamma-MG but not alpha-MG attenuated LPS-mediated IkappaB-alpha degradation and nuclear factor-kappaB (NF-kappaB) activity. In addition, gamma-MG prevented the suppression by LPS of insulin-stimulated glucose uptake and PPAR-gamma and adiponectin gene expression. Taken together, these data demonstrate that MG attenuates LPS-mediated inflammation and insulin resistance in human adipocytes, possibly by inhibiting the activation of MAPK, NF-kappaB, and AP-1.
...
PMID:Xanthones from mangosteen prevent lipopolysaccharide-mediated inflammation and insulin resistance in primary cultures of human adipocytes. 1940 22

Peroxisome proliferator-activated receptor (PPAR) transcription factors are pharmaceutical drug targets for treating diabetes, atherosclerosis, and inflammatory degenerative diseases. The possible mechanism of interaction between the three PPAR isotypes (alpha, beta/delta, and gamma) is not yet clear. However, this is important both for understanding transcription factor regulation and for the development of new drugs. The present study was designed to compare the effects of combinations of synthetic agonists of PPARalpha [2-[4-[2-[4-cyclohexylbutyl (cyclohexylcarbamoyl)amino]ethyl]phenyl] sulfanyl-2-methylpropanoic acid (GW7647)], PPARbeta/delta [4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid, (L-165041)], and PPARgamma (rosiglitazone, ciglitazone) on inflammatory gene regulation in rat primary astrocytes. We measured cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) synthesis in lipopolysaccharide (LPS)-stimulated cells. PPARalpha, PPARbeta/delta, and PPARgamma knockdown models served to delineate the contribution of each PPAR isotype. Thiazolidinediones enhanced the LPS-induced COX-2 expression via PPARgamma-dependent pathway, whereas L-165041 and GW7647 had no influence. However, the addition of L-165041 potentiated the effect of PPARgamma activation through PPARbeta/delta-dependent mechanism. On the contrary, PPARalpha activation (GW7647) suppressed the effect of the combined L-165041/rosiglitazone application. The mechanism of the interplay arising from combined applications of PPAR agonists involves changes in PPAR expression levels. A PPARbeta/delta overexpression model confirmed that PPARbeta/delta expression level is the point at which PPARgamma and PPARalpha pathways converge in control of COX-2 gene expression. Thus, we discovered that in primary astrocytes, PPARgamma has a positive influence and PPARalpha has a negative influence on PPARbeta/delta expression and activity. A positive/negative-feedback loop is formed by PPARbeta/delta-dependent increase in PPARalpha expression level. These findings elucidate a novel principle of regulation in the signaling by synthetic PPAR agonists that involves modulating the interaction between PPARalpha,-beta/delta, and -gamma isoforms on the level of their expression.
...
PMID:Peroxisome proliferator-activated receptor (PPAR)-gamma positively controls and PPARalpha negatively controls cyclooxygenase-2 expression in rat brain astrocytes through a convergence on PPARbeta/delta via mutual control of PPAR expression levels. 1948 6

Multiple factors contribute to the pathogenesis and prognosis of chronic obstructive pulmonary disease(COPD), still requiring new therapeutic strategies and medications for the disease. The aim of the present study is to investigate the model of lipopolysaccharide (LPS)-induced chronic lung injury and hyperinflation and test therapeutic effects of peroxisome proliferator-activated receptor (PPAR)-gamma agonist. Wister rats were challenged with intra-tracheal instillation of LPS at concentrations of 0.006, 0.060, 0.600, and 6.000 mg/ml per kg, twice a week, for 1, 2, 4 and 6 weeks. PPAR activator, 15-deoxy-Delta12,14-prostaglandin J2 (15D-PGJ2), or vehicle (PBS) was administered orally and daily at the dose of 1 and 10 mg/ml per kg in animals challenged with LPS or PBS at the dose of 0.060 mg/ml per kg body weight twice a week for 4 weeks. We found that intra-tracheal exposure of LPS resulted in a dose-dependent pattern of chronic lung hyperinflation and hypertrophy, increased alveolar enlargement, reduced vascular endothelial growth factor (VEGF) and elevated tissue inhibitor of metalloproteinases (TIMP)-1 levels in bronchoalveolar lavage (BAL) fluid, and early changes of leukocyte influx and interferon (IFN)-gamma levels in bronchoalveolar lavage (BAL) fluid. PPAR-gamma agonist ameliorated these changes related with the dose used.LPS-induced lung disease model shows some similarities with human disease, and PPAR-gamma agonist maybe an alternative for COPD therapy.
...
PMID:Potential effects of peroxisome proliferator-activated receptor activator on LPS-induced lung injury in rats. 1948 31

Macrophages ingesting apoptotic cells attenuate inflammatory responses, such as reactive oxygen species (ROS) generation. In atherosclerosis, ongoing inflammation and accumulation of apoptotic/necrotic material are observed, suggesting defects of phagocytes in recognizing or responding to dying cells. Modified lipoproteins such as oxidized LDL (oxLDL) are known to promote inflammation and to interfere with apoptotic cell clearance. Here, we studied the impact of cells exposed to oxLDL on their ability to interfere with the oxidative burst in phagocytes. In contrast to apoptotic cells, cells dying in response to or in the presence of oxLDL failed to suppress ROS generation despite efficiently being taken up by phagocytes. In addition, apoptotic cells, but not oxLDL-treated cells, inhibited phosphorylation of extracellular signal-regulated kinase, which is important for NADPH oxidase activation. oxLDL treatment did not interfere with activation of the antiinflammatory transcriptional regulator peroxisome proliferator-activated receptor gamma by apoptotic cells. Moreover, cells exposed to oxLDL failed to suppress lipopolysaccharide- induced proinflammatory cytokine expression, whereas apoptotic cells attenuated these phagocyte responses. Thus, the presence of oxLDL during cell death impaired the ability of apoptotic cells to act antiinflammatory with regard to oxidative burst inhibition and cytokine expression in phagocytes.
...
PMID:Attenuated suppression of the oxidative burst by cells dying in the presence of oxidized low density lipoprotein. 1949 97

Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors belonging to the nuclear receptor superfamily and are involved in the control of COX-2 expression, and vice versa. Here, we show that COX-2 promoter activity was suppressed by essential oils derived from thyme, clove, rose, eucalyptus, fennel, and bergamot in cell-based transfection assays using bovine arterial endothelial cells. Moreover, from thyme oil, we identified carvacrol as a major component of the suppressor of COX-2 expression and an activator of PPARalpha and gamma. PPARgamma-dependent suppression of COX-2 promoter activity was observed in response to carvacrol treatment. In human macrophage-like U937 cells, carvacrol suppressed lipopolysaccharide-induced COX-2 mRNA and protein expression, suggesting that carvacrol regulates COX-2 expression through its agonistic effect on PPARgamma. These results may be important in understanding the antiinflammatory and antilifestyle-related disease properties of carvacrol.
...
PMID:Carvacrol, a component of thyme oil, activates PPARalpha and gamma and suppresses COX-2 expression. 1957 62

Heme-oxygenase-1 (HO-1), an important enzyme involved in vascular disease, transplantation, and inflammation, catalyzes the degradation of heme into carbon monoxide and biliverdin. It has been reported that overexpression of HO-1 inhibits osteoclastogenesis. However, the effect of HO-1 on osteoblast differentiation is still not clear. We here used adenoviral vector expressing recombinant human HO-1 and HO-1 inducer hemin to study the effects of HO-1 in primary cultured osteoblasts. The results showed that induction of HO-1 inhibited the maturation of osteoblasts including mineralized bone nodule formation, alkaline phosphatase activity and decreased mRNA expression of several differentiation markers such as alkaline phosphatase, osteocalcin, and RUNX2. Furthermore, downstream products of HO-1, bilirubin, carbon monoxide, and iron, are involved in the inhibitory action of HO-1. HO-1 can be induced by H(2)O(2), lipopolysaccharide and inflammatory cytokines such as TNF-alpha and IL-1beta in osteoblasts and also in STZ-induced diabetic mice. In addition, endogenous PPARgamma ligand, 15-deoxy-Delta(12,14)-prostaglandin-J2 (15d-PGJ2) markedly increased both mRNA and protein levels of HO-1 in osteoblasts via PI3K-Akt and MAPK pathways. Blockade of HO activity by ZnPP IX antagonized the inhibitory action on osteocalcin expression by hemin and 15d-PGJ2. Our results indicate that upregulation of HO-1 inhibits the maturation of osteoblasts and HO-1 may be involved in oxidative- or inflammation-induced bone loss.
...
PMID:Upregulation of heme oxygenase-1 inhibits the maturation and mineralization of osteoblasts. 2002 Apr 68

Insulin resistance, the major metabolic abnormality underlying type 2 diabetes, is associated with chronic inflammation and heavy macrophage infiltration in white adipose tissue (WAT). The therapeutic properties of the synthetic adrenal steroid Delta(5)-androstene-17alpha-ethynyl-3beta,7beta,17beta-triol (HE3286) were characterized in metabolic disease models. Treatment of diabetic db/db mice with HE3286 suppressed progression to hyperglycemia and markedly improved glucose clearance. Similar effects were also observed in insulin-resistant, diet-induced obese C57BL/6J mice and genetically obese ob/ob mice. This effect appeared to be a consequence of reduced insulin resistance because HE3286 lowered blood insulin levels in db/db and ob/ob mice. Treatment with HE3286 was accompanied by suppressed expression of the prototype macrophage-attracting chemokine monocyte chemoattractant protein-1 in WAT, along with its cognate receptor C-C motif chemokine receptor-2. Exposure of mouse macrophages to HE3286 in vitro caused partial suppression of endotoxin (lipopolysaccharide)-induced nuclear factor kappa-B (NF-kappaB)-sensitive reporter gene expression, NF-kappaB nuclear translocation, and NF-kappaB/p65 serine phosphorylation. Proinflammatory kinases, including IkappaB kinase, c-Jun NH2-terminal kinase, and p38, were also inhibited by HE3286. In ligand competition experiments HE3286 did not bind to classical sex steroid or corticosteroid receptors, including androgen receptor (AR), progesterone receptor, estrogen receptor (ER) alpha or ERbeta, and glucocorticoid receptor (GR). Likewise, in cells expressing nuclear receptor-sensitive reporter genes HE3286 did not substantially stimulate transactivation of AR, ER, GR, or peroxisome proliferator-activated receptor (PPAR) alpha, PPARdelta, and PPARgamma. These findings indicate that HE3286 improves glucose homeostasis in diabetic and insulin-resistant mice and suggest that the observed therapeutic effects result from attenuation of proinflammatory pathways, independent of classic sex steroid receptors, corticosteroid receptors, or PPARs.
...
PMID:Amelioration of glucose intolerance by the synthetic androstene HE3286: link to inflammatory pathways. 2006 30

Peroxisome proliferator-activated receptor gamma (PPARgamma) gained considerable interest as a therapeutic target during chronic inflammatory diseases. Remarkably, the pathogenesis of diseases such as multiple sclerosis or Alzheimer is associated with impaired PPARgamma expression. Considering that regulation of PPARgamma expression during inflammation is largely unknown, we were interested in elucidating underlying mechanisms. To this end, we initiated an inflammatory response by exposing primary human macrophages to lipopolysaccharide (LPS) and observed a rapid decline of PPARgamma1 expression. Because promoter activities were not affected by LPS, we focused on mRNA stability and noticed a decreased mRNA half-life. As RNA stability is often regulated via 3'-untranslated regions (UTRs), we analyzed the impact of the PPARgamma-3'-UTR by reporter assays using specific constructs. LPS significantly reduced luciferase activity of the pGL3-PPARgamma-3'-UTR, suggesting that PPARgamma1 mRNA is destabilized. Deletion or mutation of a potential microRNA-27a/b (miR-27a/b) binding site within the 3'-UTR restored luciferase activity. Moreover, inhibition of miR-27b, which was induced upon LPS exposure, partially reversed PPARgamma1 mRNA decay, whereas miR-27b overexpression decreased PPARgamma1 mRNA content. In addition, LPS further reduced this decay. The functional relevance of miR-27b-dependent PPARgamma1 decrease was proven by inhibition or overexpression of miR-27b, which affected LPS-induced expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-6. We provide evidence that LPS-induced miR-27b contributes to destabilization of PPARgamma1 mRNA. Understanding molecular mechanisms decreasing PPARgamma might help to better appreciate inflammatory diseases.
...
PMID:MicroRNA-27b contributes to lipopolysaccharide-mediated peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA destabilization. 2016 87


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

---