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)

Heme-oxygenase-1 (HO-1) is an inducible cytoprotective molecule that displays antioxidant, antiapoptotic, and antiinflammatory effects. In addition, HO-1 appears to have a complex role in angiogenesis. Recent in vivo studies report that vascular endothelial growth factor (VEGF) regulates HO-1 expression and activity in vascular endothelial cells (ECs) and that inhibition of HO-1 abrogates VEGF-induced endothelial activation and subsequent angiogenesis, while promoting VEGF-induced monocyte recruitment and inflammatory angiogenesis. HO-1 may also regulate the synthesis and activity of VEGF, resulting in a positive-feedback loop. In contrast, HO-1 activity has the opposite effect on lipopolysaccharide-driven inflammatory angiogenesis, inhibiting leukocyte invasion and preventing subsequent angiogenesis. In this review, we summarize the current understanding of the role of HO-1 in angiogenesis. We conclude that further investigation, using targeted molecular approaches specifically to alter HO-1 activity, are required to develop our understanding of the role of HO-1 and its products, carbon monoxide, biliverdin, bilirubin, and free iron in angiogenesis. We propose that during chronic inflammation, HO-1 has two roles, first an antiinflammatory action inhibiting leukocyte infiltration, and second, promotion of VEGF-driven noninflammatory angiogenesis, which facilitates tissue repair. Additional studies will help determine whether modulating the activity of HO-1 and/or its products has therapeutic potential in chronic inflammatory dise.
 ...
PMID:Dual role of VEGF-induced heme-oxygenase-1 in angiogenesis. 1691 Jul 63

Corneal neovascularization can be induced by a severe ocular infection, injury or immunological diseases. The vascular endothelial growth factor (VEGF) is the main cytokine involved in this phenomenon, inducing angiogenesis from the vascularized ocular tissues. As the limbal tissue is located between conjunctival and corneal tissues, we suggest that the limbal cells are participating in the production of VEGF induced by bacterial components as LPS. In this work, RT-PCRs and immunoblots were used to investigate the expression of VEGF and other pro-angiogenic genes in primary cultures of human limbal fibroblasts (PCHLF) treated with lipopolysaccharide (LPS) from Escherichia coli. We found that the expression of VEGF was initiated at 6 h and reaches its highest expression at 72 h after stimulation with LPS. Up-regulation of toll-like receptor 4 (TLR4) after 3 h of treatment was also observed. LPS-induced the expression of VEGF in a dose-dependent manner, and the blocking of TLR4 with an anti-TLR4 antibody prevented VEGF expression. We also analyzed the molecules that modulate VEGF expression. LPS did not induce the up-regulation of LL-37 nor the hypoxia induced factor 1 alpha (HIF-1alpha) mRNA expression, however, an up-regulation of interleukin 13 receptor alpha 1 (IL-13Ralpha1) and interleukin 4 receptor alpha (IL-4Ralpha) were observed after 3 and 12 h of stimulation, respectively. The expression of interleukin 13 did not change throughout the treatment. These results suggest that TLR4, IL-13Ralpha1 and IL-4Ralpha induced by LPS in PCHLF could be playing an important role in the corneal neovascularization.
 ...
PMID:Lipopolysaccharide from Escherichia coli induces the expression of vascular endothelial growth factor via toll-like receptor 4 in human limbal fibroblasts. 1699 97

Bactericidal/permeability-increasing protein (BPI) was originally identified as a lipopolysaccharide (LPS) binding protein with gram-negative bactericidal activity in the leukocytes. In this study, we characterized the previously unknown effects of BPI in the eye and the molecular mechanisms involved in its action. BPI mRNA was detected in bovine retina; retinal pigment epithelium; and primary cultures of bovine retinal pigment epithelial cells (RPE), pericytes (RPC), and endothelial cells (REC); while BPI protein was measured in human vitreous and plasma. BPI, but not control protein thaumatin, activated extracellular regulated kinase (ERK) and AKT, and increased DNA synthesis in RPE and RPC but not in REC. A human recombinant 21 kDa modified amino-terminal fragment of BPI (rBPI21) reduced H2O2-induced apoptosis in RPE and inhibited vascular endothelial growth factor (VEGF)-stimulated ERK phosphorylation in REC when preincubated with VEGF. Intraperitoneal (i.p.)-injected rBPI21 reduced ischemia-induced retinal neovascularization and diabetes-induced retinal permeability. Since BPI has unusual dual properties of promoting RPC and RPE growth while suppressing VEGF-induced REC growth and vascular permeability, the mechanistic understanding of BPI's action may provide novel therapeutic opportunities for diabetic retinopathy and age-related macular degeneration.
 ...
PMID:Bactericidal/permeability-increasing protein's signaling pathways and its retinal trophic and anti-angiogenic effects. 1701 58

Macrophages are an important source of vascular endothelial growth factor (VEGF). Adenosine A2A receptor (A2AR) agonists with Toll-like receptor (TLR) 2, 4, 7, and 9 agonists synergistically induce macrophage VEGF expression. We show here using VEGF promoter-luciferase reporter constructs that the TLR4 agonist Escherichia coli lipopolysaccharide (LPS) and the A2AR agonists NECA and CGS21680 synergistically augment VEGF transcription in macrophages and that the HRE in the VEGF promoter is essential for this transcription. We examined whether LPS and/or NECA induce HIF-1alpha expression. HIF-1alpha mRNA levels were increased in LPS-treated macrophages in an NF-kappaB-dependent manner; NECA strongly increased these levels in an A2AR-dependent manner. LPS induced luciferase expression from a HIF-1alpha promoter-luciferase construct in an A2AR-independent manner. Further stimulation with NECA did not increase HIF-1alpha promoter activity, indicating that the A2AR-dependent increase in HIF-1alpha mRNA is post-transcriptional. LPS/NECA treatment also increased HIF-1alpha protein and DNA binding levels. Deletion of putative NF-kappaB-binding sites from the VEGF promoter did not affect LPS/NECA-induced VEGF promoter activity, suggesting that NF-kappaB is not directly involved in VEGF transcription. Taken together, these data indicate that LPS/NECA-induced VEGF expression involves transcriptional regulation of the VEGF promoter by HIF-1alpha through the HRE. HIF-1alpha is transcriptionally induced by LPS and post-transcriptionally up-regulated in an A2AR-dependent manner.
 ...
PMID:Synergistic up-regulation of vascular endothelial growth factor (VEGF) expression in macrophages by adenosine A2A receptor agonists and endotoxin involves transcriptional regulation via the hypoxia response element in the VEGF promoter. 1706 55

Dendritic cells (DCs) are the most potent antigen-presenting cells and play a central role in the host-antitumor immunity. Since it has been reported that vascular endothelial growth factor (VEGF) inhibits the functional maturation of immature-DCs and impairs DC differentiation, it is important to elucidate the mechanisms of VEGF-induced DC-dysfunction. To investigate the effects of VEGF against human mature DCs, we investigated how VEGF affects mature DCs with regards to phenotype, induction of apoptosis, IL-12(p70) production and the antigen-presenting function evaluated by allogeneic mixed leukocyte reaction (allo-MLR). We generated monocyte-derived DCs matured with lipopolysaccharide, OK-432 or pro-inflammatory cytokine cocktails. As a result, VEGF treatment did not alter the mature DCs with regard to phenotype, IL-12(p70) production and induction of apoptosis. As a novel and important finding, VEGF inhibited the ability of mature DCs to stimulate allogeneic T cells. Furthermore, this VEGF-induced DC dysfunction was mainly mediated by VEGF receptor-2 (VEGF R2). These observations were confirmed by the findings that the VEGF-induced DC dysfunction was recovered by anti-human VEGF neutralizing mAb or anti-human VEGF R2 blocking mAb, and that placenta growth factor (PlGF), VEGF R1-specific ligand, did not have any effect against mature DCs. Some modalities aiming at reversing mature-DC dysfunction induced by VEGF will be needed in order to induce the effective antitumor immunity.
 ...
PMID:Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2. 1708 23

Unlike the tocopherols, the tocotrienols, also members of the vitamin E family, have an unsaturated isoprenoid side chain. In contrast to extensive studies on tocopherol, very little is known about tocotrienol. Because the nuclear factor-kappaB (NF-kappaB) pathway has a central role in tumorigenesis, we investigated the effect of gamma-tocotrienol on the NF-kappaB pathway. Although gamma-tocotrienol completely abolished tumor necrosis factor alpha (TNF)-induced NF-kappaB activation, a similar dose of gamma-tocopherol had no effect. Besides TNF, gamma-tocotrienol also abolished NF-kappaB activation induced by phorbol myristate acetate, okadaic acid, lipopolysaccharide, cigarette smoke, interleukin-1beta, and epidermal growth factor. Constitutive NF-kappaB activation expressed by certain tumor cells was also abrogated by gamma-tocotrienol. Reducing agent had no effect on the gamma-tocotrienol-induced down-regulation of NF-kappaB. Mevalonate reversed the NF-kappaB inhibitory effect of gamma-tocotrienol, indicating the role of hydroxymethylglutaryl-CoA reductase. Gamma-tocotrienol blocked TNF-induced phosphorylation and degradation of IkappaBalpha through the inhibition of IkappaBalpha kinase activation, thus leading to the suppression of the phosphorylation and nuclear translocation of p65. gamma-Tocotrienol also suppressed NF-kappaB-dependent reporter gene transcription induced by TNF, TNFR1, TRADD, TRAF2, TAK1, receptor-interacting protein, NIK, and IkappaBalpha kinase but not that activated by p65. Additionally, the expressions of NF-kappaB-regulated gene products associated with antiapoptosis (IAP1, IAP2, Bcl-xL, Bcl-2, cFLIP, XIAP, Bfl-1/A1, TRAF1, and Survivin), proliferation (cyclin D1, COX2, and c-Myc), invasion (MMP-9 and ICAM-1), and angiogenesis (vascular endothelial growth factor) were down-regulated by gamma-tocotrienol. This correlated with potentiation of apoptosis induced by TNF, paclitaxel, and doxorubicin. Overall, our results demonstrate that gamma-tocotrienol inhibited the NF-kappaB activation pathway, leading to down-regulation of various gene products and potentiation of apoptosis.
 ...
PMID:Gamma-tocotrienol inhibits nuclear factor-kappaB signaling pathway through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and potentiation of apoptosis. 1711 79

Progenitor cell plasticity enhances positive remodeling of damaged tissue. We and others have previously shown that progenitor cells may limit apoptosis and modulate inflammation in part by the production of growth factors. However, recent studies suggest that progenitor cells senesce and lose their differentiation potential with increasing time in culture and passage. We hypothesize that murine bone marrow mesenchymal stem cells (MSCs) are cardioprotective against ischemia/reperfusion injury in the isolated perfused rat heart, and that passage number has an adverse effect on MSC activation and cardioprotection. Adult male and female Sprague-Dawley rat hearts were isolated, perfused via Langendorff model, and subjected to ischemia/reperfusion. Mouse MSCs were harvested, cultured, suspended in perfusate, and infused before global index ischemia. Hearts were assigned to controls or infusion with passage 3, 5, or 10 MSCs. In addition, MSCs in culture were stressed by hypoxia and increasing doses of endotoxin (lipopolysaccharide). Mesenchymal stem cell activation was determined by measuring vascular endothelial growth factor production with enzyme-linked immunosorbent assay. All data are reported as mean +/- SEM and were analyzed with 2-way analysis of variance. Differences are considered significant if P < 0.05. Passage 3 murine MSC infusion in hearts before ischemia reduced the depression of left ventricular developed pressure, attenuated the increase of end-diastolic pressure, and reduced the depression of +dP/dT and -dP/dT. However, the MSC protective effect disappeared in hearts infused with passage 5 and passage 10 MSCs. Although hypoxia and lipopolysaccharide resulted in significant activation of MSCs, passage 3 MSCs demonstrated significantly greater vascular endothelial growth factor release than passage 5 and 10 MSCs. Acute murine MSC infusion confers protection in isolated rat hearts. However, high passage number has an adverse effect on MSC activation and protection. This portends limited ex vivo expansion before possible therapeutic use.
 ...
PMID:High passage number of stem cells adversely affects stem cell activation and myocardial protection. 1711 32

Porphyromonas gingivalis is a major periodontal pathogen. The lipopolysaccharide (LPS) secreted from P. gingivalis is implicated in the initiation and progression of periodontitis. Aberrant angiogenesis is often associated with lesion formation in chronic periodontitis. In this study, we report that P. gingivalis LPS activates angiogenic cascade, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs). Furthermore, P. gingivalis LPS potently stimulated in vivo neovascularization in chick chorioallantoic membrane (CAM) and the mouse Matrigel plug assay. P. gingivalis LPS had no effect on the expression of vascular endothelial growth factor (VEGF) or its receptor, Flk-1, implying that P. gingivalis LPS-induced angiogenesis may result from its direct action on endothelial cells. P. gingivalis LPS evoked activation of the mitogen-activated protein kinase ERK1/2 in HUVECs, which is closely linked to angiogenesis. Taken together, these results strongly suggest P. gingivalis LPS plays an important role in the pathological angiogenesis for periodontal diseases, such as periodontitis.
 ...
PMID:Porphyromonas gingivalis, periodontal pathogen, lipopolysaccharide induces angiogenesis via extracellular signal-regulated kinase 1/2 activation in human vascular endothelial cells. 1732 40

Agents that increase natural protective mechanisms have been proposed for the prevention and treatment of intramammary infections. Staphylococcus aureus is a major pathogen causing primarily subclinical chronic mastitis that responds poorly to antibiotic therapy. The objectives of this study were to describe the effects of a single intramammary infusion of a lipopolysaccharide-based biological response modifier (BRM) on mammary epithelial cellular proliferation and expression of insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in uninfected and Staph. aureus-infected bovine mammary glands during involution. Three groups of 12 cows, 6 Staph. aureus-infected and 6 uninfected, were infused with BRM or placebo in 2 mammary quarters and killed at 7, 14, and 21 d of involution. The proportion of infected quarters, mammary cell proliferation, and IGF-I and VEGF expression were evaluated. Biological response modifier treatment decreased the proportion of Staph. aureus-infected mammary quarters at 7 d of involution, but a similar number of isolations were observed at 14 and 21 d of involution in either treated or control quarters. The percentage of proliferating mammary epithelial cells was higher in infected than uninfected quarters at every observation period, irrespective of the treatment administered, whereas uninfected BRM-treated quarters showed increased cell proliferation at 7 d of involution. Insulin-like growth factor-I expression in uninfected quarters was not affected by treatment and showed a decrease at 21 d of involution. Expression of IGF-I was greater in infected than uninfected quarters at every observation period, irrespective of the treatment received. Expression of VEGF was greater in BRM-treated uninfected quarters at 7 d of involution compared with controls. In infected quarters, VEGF expression was lowest in BRM-treated quarters at 7 d of involution and increased throughout the observation period. Conversely, untreated infected quarters showed the highest VEGF expression at 7 d and decreased at 21 d of involution. Mammary cell proliferation and expression of IGF-I and VEGF were increased in Staph. aureus-infected quarters. Increased mammary cell proliferation and VEGF expression were observed in BRM-treated quarters during the first week of involution.
 ...
PMID:Effect of a biological response modifier on expression of growth factors and cellular proliferation at drying off. 1743 Sep 22

Little is known concerning the possible contribution of T helper 2 (Th2)-type cytokines to the recruitment of neutrophils into the lung tissue. In the present study, endothelial cells from equine pulmonary arteries were cultured in the presence of recombinant equine (re) IL-4 and reIL-5, and the cytokine mRNA expression of molecules implicated in the chemotaxis and migration of neutrophils was studied using real-time RT-PCR. The functional response of reIL-4-induced endothelial cell stimulation on neutrophil migration was also studied using a chemotaxis chamber. ReIL-4 either increased the expression of CXCL-8, E-selectin, vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS), or potentiated the coeffects of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) on CXCL-8. Supernatants collected from cultured endothelial cells stimulated with reIL-4 significantly promoted neutrophil migration in a dose-dependent manner. Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS. DXM and 1400W attenuated the mRNA expression of E-selectin and iNOS induced by the costimulation of reIL-4, reTNF-alpha, and LPS. Neither equine nor human recombinant IL-5 influenced the mRNA expression of CXCL-8, E-selectin, or VEGF. These findings suggest that Th2-type cytokines may contribute to pulmonary neutrophilia during allergic inflammation by the increased expression of neutrophil chemokines and adhesion molecules by endothelial cells. DXM and the iNOS inhibitors may decrease pulmonary neutrophilia due, in part, to a direct inhibition of some of these factors.
 ...
PMID:IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells. 1749 51


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