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)

Extracorporeal shock wave treatment appears to be effective in patients with avascular necrosis of the femoral head. However, the pathway of biological events whereby this is accomplished has not been fully elucidated. The purpose of this study was to investigate the effect of extracorporeal shock waves on vascular endothelial growth factor (VEGF) expression in necrotic femoral heads of rabbits. VEGF expression was assessed by immunohistochemistry, quantitative real-time PCR, and Western blot analysis. The degree of angiogenesis was also assessed, as determined by the microvessel density (MVD), the assessment of which was based on CD31-expressing vessels. Bilateral avascular necrosis of femoral heads was induced with methylprednisolone and lipopolysaccharide in 30 New Zealand rabbits. The left limb (the study side) received shock wave therapy to the femoral head. The right limb (the control side) received no shock wave therapy. Biopsies of the femoral heads were performed at 1, 2, 4, 8, and 12 weeks. Western blot analysis and real-time PCR showed that shock wave therapy significantly increased VEGF protein and mRNA expression, respectively, in the subchondral bone of the treated necrotic femoral heads. Compared with the contralateral control without shock wave treatment, the VEGF mRNA expression levels increased to a peak at 2 weeks after the shock wave treatment and remained high for 8 weeks, then declined at 12 weeks, whereas the VEGF protein expression levels increased to a peak at 4 weeks after the shock wave treatment and remained high for 12 weeks. The immunostaining of VEGF was weak in the control group, and the immunoreactivity level in the shock-wave-treated group increased at 4 weeks and persisted for 12 weeks. The most intensive VEGF immunoreactivity was observed in the proliferative zone above the necrotic zone. At 4, 8, and 12 weeks after the shock wave treatment, MVD in subchondral bone from treated femoral heads was significantly higher than that in subchondral bone from untreated femoral heads. These data clearly show that extracorporeal shock waves can significantly upregulate the expression of VEGF. The upregulation of VEGF may play a role in inducing the ingrowth of neovascularization and in improving the blood supply to the femoral head.
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PMID:Upregulation of VEGF in subchondral bone of necrotic femoral heads in rabbits with use of extracorporeal shock waves. 1762 36

Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust-derived PM affects dendritic cell (DC) activation. DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). DC were stimulated for 48 hours with CEP, DEP, CD40-ligand, or lipopolysaccharide. DC activation was assessed by flow cytometry, enzyme-linked immunosorbent assay, and standard culture techniques. DEP increased uptake of fluorescein isothiocyanate-dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g., CD40 [P < 0.01] and MHC class II [P < 0.01]). By contrast, CEP poorly affected antigen uptake and expression of cell surface molecules, and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6, and IFN-gamma (P < 0.01), IL-12 (P < 0.05), and vascular endothelial growth factor (P < 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN-gamma production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser extent CEP) regulate important functional aspects of human DC, supporting an adjuvant role for this material.
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PMID:Diesel-enriched particulate matter functionally activates human dendritic cells. 1763 Mar 18

In this study, we show that activation of toll-like receptor (TLR)4 by lipopolysaccharide (LPS) induces cyclooxygenase-2 (COX-2) expression, which results in prostaglandin (PG)I2 formation in macrophages. The LPS-stimulated COX-2 expression and PGI2 release were accompanied by production of the potent angiogenic cytokine, vascular endothelial growth factor (VEGF), and these effects were suppressed by NS-398, which is a COX-2 inhibitor. Direct addition of iloprost (an analogue of PGI2) for IP receptor also induced the production of VEGF, whereas DP, FP, and TP receptor agonists did not. Inhibition of IP protein expression by micro interfering RNA blocked LPS-induced VEGF production. Additionally, macrophages transiently caused Akt phosphorylation after stimulation with LPS, and inhibition of Akt phosphorylation blocked the production of VEGF and COX-2 expression in response to LPS. Overall, this study demonstrated that engagement of TLR4 with LPS induces production of PGI2 via Akt and generates VEGF through IP receptor.
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PMID:Activation of toll-like receptor 4 modulates vascular endothelial growth factor synthesis through prostacyclin-IP signaling. 1782 54

Studies using animal models of peritoneal dialysis (PD) have commonly induced acute peritonitis by intraperitoneal (IP) administration of lipopolysaccharide (LPS). We compared the effects of peritonitis induced by IP administration of either LPS or zymosan on inflammatory parameters [dialysate leukocyte counts and dialysate concentrations of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF)] and peritoneal transport of fluid, small solutes (glucose), and macromolecules (total protein) in a mouse model of PD. Eighteen hours after induction of peritonitis, mice were studied by injecting 2 mL of 4.25% dextrose-containing PD solution into the peritoneal cavity for a 2-hour dwell. Concentrations of glucose, total protein, PGE2, and VEGF were determined in the dialysate effluent. Acute peritonitis induced by IP administration of LPS induced changes in peritoneal transport similar to those observed during clinical PD, but without a significant increase in the dialysate leukocyte count. In contrast, acute peritonitis induced by IP administration of zymosan induced a large increase in dialysate leukocyte count, more substantial changes in peritoneal transport, and increases in dialysate PGE2 and VEGF concentrations. We conclude that acute peritonitis induced by IP administration of zymosan in the mouse may be a more relevant model for clinical PD, because it produces substantial changes in peritoneal transport and leukocyte migration into the peritoneal cavity.
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PMID:Acute peritonitis in a C57BL/6 mouse model of peritoneal dialysis. 1788 6

LDL-apheresis (LA) was originally used for familial hyperlipidemia, and then in Japan extended to use for the treatment of patients with peripheral arterial disease (PAD) and nephrotic syndrome due to steroid-resistant focal glomerular sclerosis (FGS). The reason why this treatment is applicable for these disorders is due to the fact that LA exerts its favorable effects beyond the lipid-lowering effect. The main underlying mechanisms, for example, in the case of LA application in patients with PAD are: (1) improvement of hemorheology, (2) improvement of endothelial dysfunction, (3) elevations of serum levels of NO and bradykinin, (4) increase in serum levels of vascular endothelial growth factor, and (5) reduction of adhesion molecules on monocytes. Furthermore, we have reported that LA could have anti-inflammatory effects because LA reduces serum levels of P-selectin, which is known to play an important role in the development of atherosclerosis as well as a reduction of serum C-reactive protein levels as standard biomarker of atherosclerosis. Massive proteinuria is also an important challenge in nephrology. The possible mechanisms besides removal of toxic lipids are the reduction of the vasoconstrictive prostanoid and thromboxane A2 (TXA2) and an improvement in macrophage function evidenced by a significant amelioration of interleukin-8 production by lipopolysaccharide-stimulated peripheral blood mononuclear cells. It is intriguing to note that in terms of pharmacodynamics, LA improves steroid and cyclosporine uptake into lymphocytes. Although there are no randomized controlled trials, it is clear that LA has various effects beyond lowering lipids. Making the device more concise and changing it into a whole blood adsorption type, we need to collect more clinical cases and to study the underlying mechanisms further.
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PMID:Applications of LDL-apheresis in nephrology. 1817 56

We investigated the gene expression profiles of vascular endothelial growth factor (VEGF) and its receptors in HL-60 leukemia cells. In the VEGF family, both mRNA and protein expression of VEGF-C were up-regulated in phorbol myristate acetate (PMA)-differentiated HL-60 cells. We detected two bands of approximately 31 and approximately 60kDa in cell lysates, and the higher expression of approximately 31kDa band was further increased after stimulation with tumor necrosis factor (TNF)-alpha and lipopolysaccharide (LPS). A approximately 31kDa VEGF-C protein was also detected in conditioned media from PMA-differentiated HL-60 cells after LPS stimulation. The mRNA expression of VEGFR-1, VEGFR-2, and neuropilin-1 (NRP-1) was markedly up-regulated in PMA-differentiated HL-60 cells, corresponding to the results from VEGF binding studies, in which VEGF binding activity was increased in PMA-differentiated HL-60 cells. These did not occur in dimethylsulfoxide (DMSO)-differentiated HL-60 cells. The expression of VEGF-C and VEGF receptors is regulated specifically in HL-60 cells during macrophage differentiation.
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PMID:Specific association of increased vascular endothelial growth factor expression and its receptors with macrophage differentiation of HL-60 leukemia cells. 1826 85

Some reports published from 1967 to 1999 describe the use of ointments containing high doses (0.1 to 0.2%, w/w) C. asiataica herb extracts to enhance wound repair. Lower doses at which burn wound repair is enhanced by such topical applications have not been established yet. We found that the application of asiaticoside at low doses of 10(-8) to 10(-12)% (w/w) facilitated burn wound repair. To clarify the accelerating mechanisms of asiaticoside on burn wound repair, we examined the effects of asiaticoside on the levels of various cytokines produced at the site of the burn wound. The topical application of a low dose (10 pg, 1 ng, or 100 ng/wound area) of asiaticoside increased monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and interleukin (IL)-1beta levels in burn wound exudates. Asiaticoside (10 pg to 100 ng/ml) enhanced MCP-1 production in HaCaT cells, but it had no direct effect on VEGF production. Furthermore, asiaticoside (10 pg to 100 ng/ml) increased the IL-1beta production in THP-1 macrophages with MCP-1, but it had no effect on IL-1beta production without MCP-1 or with lipopolysaccharide (LPS). These findings suggest that the enhancement of burn wound healing by asiaticoside might be due to the promotion of angiogenesis during skin wound repair as a result of the stimulation of VEGF production caused by the increase in MCP-1 expression in keratinocytes and the increase in IL-1beta expression in macrophages induced cooperatively by asiaticoside plus MCP-1.
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PMID:Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism. 1835 10

Lipoxin A(4) (LXA(4)) is a lipid mediator that plays an important role in inflammation resolution. We assessed the anti-inflammatory effect of LXA(4) on endotoxin-induced uveitis (EIU) in rats. The inflammatory cell number and levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)), and protein, as well as expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), in the anterior chamber of the eye were determined 24 h after lipopolysaccharide (LPS; 200 mug/paw) intradermal injection. The immunohistochemical reactivities of nuclear factor-kappaB (NF-kappaB) and c-Jun were also examined. Topical LXA(4) (1-10 ng/eye) pretreatment decreased the number of inflammatory cells and the protein leakage into the aqueous humor (AqH). In addition, topical LXA(4) (10 ng/eye) inhibited the LPS-induced production of IL-1beta, TNF-alpha, and PGE(2), and expression of COX-2 and VEGF. A decreased activation of NF-kappaB and c-Jun was also found in LXA(4)-treated eyes. It is very interesting that an anti-inflammatory effect was achieved even when LXA(4) (10 ng/eye) was applied topically after LPS challenge, as indicated by the reduction in the cellular and protein extravasations into the AqH. Moreover, topical treatment of corticosteroid prednisolone (200 mug/eye) beginning before or after LPS injection reduced all of the molecular and biochemical alterations promoted on EIU rats in an efficacy similar to that of LXA(4). Together, the present results provide clear evidence that pharmacological activation of LXA(4) signaling pathway potently reduces the EIU in rats. Therefore, LXA(4) stable analogs could represent promising agents for the management of ocular inflammatory diseases.
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PMID:Molecular mechanisms of topical anti-inflammatory effects of lipoxin A(4) in endotoxin-induced uveitis. 1841 58

Heat shock protein 90 (hsp90) inhibitors inactivate and/or degrade various client proteins, including many involved in inflammation. Increased vascular permeability is a hallmark of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Thus, we tested the hypothesis that hsp90 inhibitors may prevent and/or restore endothelial cell (EC) permeability after injury. Exposure of confluent bovine pulmonary arterial endothelial cell (BPAEC) monolayer to TGF-beta1, thrombin, bacterial lipopolysaccharide (LPS), or vascular endothelial growth factor (VEGF) increased BPAEC permeability, as revealed by decreased transendothelial electrical resistance (TER). Treatment of injured endothelium with hsp90 inhibitors completely restored TER of BPAEC. Similarly, preincubation of BPAEC with hsp90 inhibitors prevented the decline in TER induced by the exposure to thrombin, LPS, VEGF, or TGF-beta1. In addition, hsp90 inhibitors restored the EC barrier function after PMA or nocodazole-induced hyperpermeability. These effects of the hsp90 inhibitors were associated with the restoration of TGF-beta1- or nocodazole-induced decrease in VE-cadherin and beta-catenin expression at EC junctions. The protective effect of hsp90 inhibitors on TGF-beta1-induced hyperpermeability was critically dependent upon preservation of F-actin cytoskeleton and was associated with the inhibition of agonist-induced myosin light chain (MLC) and myosin phosphatase target subunit 1 (MYPT1) phosphorylation, F-actin stress fibers formation, microtubule disassembly, increase in hsp27 phosphorylation, and association of hsp90 with hsp27, but independent of p38MAPK activity. We conclude that hsp90 inhibitors exert barrier protective effects on BPAEC, at least in part, via inhibition of hsp27-mediated, agonist-induced cytoskeletal rearrangement, and therefore may have useful therapeutic value in ALI, ARDS, and other pulmonary inflammatory disease.
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PMID:Heat shock protein 90 inhibitors protect and restore pulmonary endothelial barrier function. 1847 72

The effect of thalidomide on epidermal growth factor (EGF)-induced cell growth was examined. Thalidomide inhibited EGF-induced cell growth in mouse and human monocytic leukemia cells, RAW 264.7, U937 and THP-1. Thalidomide inhibited EGF-induced phosphorylation of extracellular signal regulated kinase (ERK) 1/2, but not p38 and stress-activated protein kinase (SAPK)/JNK. The phosphorylation of MEK1/2 and Raf at Ser 338 as the upstream molecules of ERK 1/2 was also prevented by thalidomide. Further, it inhibited EGF-induced Ras activation through preventing the transition to GTP-bound active Ras. Thalidomide inhibited the Ras activation induced by lipopolysaccharide (LPS) and vascular endothelial growth factor (VEGF) as well as EGF. There was no significant difference in the expression and function of EGF receptor between thalidomide-treated and non-treated cells. Therefore, thalidomide was suggested to inhibit EGF-induced cell growth via inactivation of Ras.
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PMID:Thalidomide inhibits epidermal growth factor-induced cell growth in mouse and human monocytic leukemia cells via Ras inactivation. 1866 73


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