The Experts below are selected from a list of 30 Experts worldwide ranked by ideXlab platform
Corinne M. Spickett - One of the best experts on this subject based on the ideXlab platform.
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Toll-like receptor 4 signalling is neither sufficient nor required for Oxidised Phospholipid mediated induction of interleukin-8 expression
Atherosclerosis, 2006Co-Authors: Clett Erridge, David J. Webb, Corinne M. SpickettAbstract:Toll-like receptor (TLR)-4 signalling has been shown to accelerate atherosclerosis. As Oxidised Phospholipids are present in atherosclerotic plaque and have been shown to modulate TLR4 signalling, we investigated the role of Oxidised 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (OxPAPC) in the regulation of TLR 1, 2, 4 and 6 signalling. Unlike established TLR agonists, OxPAPC did not induce NF-?B-dependent gene expression in monocytic THP-1 cells, human aortic endothelial cells or TLR-deficient HEK-293 cells transfected with TLRs 1, 2, 4 or 6. OxPAPC induction of IL-8 was not blocked by the TLR4 specific antagonist Rhodobacter sphaeroides LPS in human aortic endothelial cells, though OxPAPC potently inhibited TLR4 mediated IL-8 induction in these cells. OxPAPC upregulated IL-8 production in TLR4 deficient HEK-293 cells and this was not increased following TLR4 overexpression. Lipids extracted from carotid atherectomy samples did not stimulate TLR 1, 2, 4 or 6 signalling in a HEK-293 transfection assay. TLR4 signalling does not contribute to OxPAPC induced IL-8 expression in human epithelial HEK-293, monocytic THP-1 or aortic endothelial cells. As lipids extracted from diseased human artery also induced no TLR signalling, it is likely that the TLR-activating materials contributing to atherosclerosis are not of endogenous lipid origin.
Clett Erridge - One of the best experts on this subject based on the ideXlab platform.
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Toll-like receptor 4 signalling is neither sufficient nor required for Oxidised Phospholipid mediated induction of interleukin-8 expression
Atherosclerosis, 2006Co-Authors: Clett Erridge, David J. Webb, Corinne M. SpickettAbstract:Toll-like receptor (TLR)-4 signalling has been shown to accelerate atherosclerosis. As Oxidised Phospholipids are present in atherosclerotic plaque and have been shown to modulate TLR4 signalling, we investigated the role of Oxidised 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (OxPAPC) in the regulation of TLR 1, 2, 4 and 6 signalling. Unlike established TLR agonists, OxPAPC did not induce NF-?B-dependent gene expression in monocytic THP-1 cells, human aortic endothelial cells or TLR-deficient HEK-293 cells transfected with TLRs 1, 2, 4 or 6. OxPAPC induction of IL-8 was not blocked by the TLR4 specific antagonist Rhodobacter sphaeroides LPS in human aortic endothelial cells, though OxPAPC potently inhibited TLR4 mediated IL-8 induction in these cells. OxPAPC upregulated IL-8 production in TLR4 deficient HEK-293 cells and this was not increased following TLR4 overexpression. Lipids extracted from carotid atherectomy samples did not stimulate TLR 1, 2, 4 or 6 signalling in a HEK-293 transfection assay. TLR4 signalling does not contribute to OxPAPC induced IL-8 expression in human epithelial HEK-293, monocytic THP-1 or aortic endothelial cells. As lipids extracted from diseased human artery also induced no TLR signalling, it is likely that the TLR-activating materials contributing to atherosclerosis are not of endogenous lipid origin.
David J. Webb - One of the best experts on this subject based on the ideXlab platform.
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Toll-like receptor 4 signalling is neither sufficient nor required for Oxidised Phospholipid mediated induction of interleukin-8 expression
Atherosclerosis, 2006Co-Authors: Clett Erridge, David J. Webb, Corinne M. SpickettAbstract:Toll-like receptor (TLR)-4 signalling has been shown to accelerate atherosclerosis. As Oxidised Phospholipids are present in atherosclerotic plaque and have been shown to modulate TLR4 signalling, we investigated the role of Oxidised 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (OxPAPC) in the regulation of TLR 1, 2, 4 and 6 signalling. Unlike established TLR agonists, OxPAPC did not induce NF-?B-dependent gene expression in monocytic THP-1 cells, human aortic endothelial cells or TLR-deficient HEK-293 cells transfected with TLRs 1, 2, 4 or 6. OxPAPC induction of IL-8 was not blocked by the TLR4 specific antagonist Rhodobacter sphaeroides LPS in human aortic endothelial cells, though OxPAPC potently inhibited TLR4 mediated IL-8 induction in these cells. OxPAPC upregulated IL-8 production in TLR4 deficient HEK-293 cells and this was not increased following TLR4 overexpression. Lipids extracted from carotid atherectomy samples did not stimulate TLR 1, 2, 4 or 6 signalling in a HEK-293 transfection assay. TLR4 signalling does not contribute to OxPAPC induced IL-8 expression in human epithelial HEK-293, monocytic THP-1 or aortic endothelial cells. As lipids extracted from diseased human artery also induced no TLR signalling, it is likely that the TLR-activating materials contributing to atherosclerosis are not of endogenous lipid origin.
Webb D.j. - One of the best experts on this subject based on the ideXlab platform.
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Oxidised Phospholipid inhibition of toll-like receptor (TLR) signalling is restricted to TLR2 and TLR4 - roles for CD14, LPS-binding protein and MD2 as targets for specificity of inhibition
American Society for Biochemistry and Molecular Biology Inc., 2008Co-Authors: Erridge C., Kennedy S., Spickett C.m., Webb D.j.Abstract:The generation of reactive oxygen species is a central feature of inflammation that results in the oxidation of host Phospholipids. Oxidised Phospholipids, such as 1-palmitoyl-2-arachidonyl-<i>sn</i>-glycero-3-phosphorylcholine (OxPAPC), have been shown to inhibit signalling induced by bacterial lipopeptide (BLP) or LPS, yet the mechanisms responsible for the inhibition of TLR-signalling by OxPAPC remain incompletely understood. Here, we examined the mechanisms by which OxPAPC inhibits TLR-signalling induced by diverse ligands in macrophages, smooth muscle cells and epithelial cells. OxPAPC inhibited TNF-α production, IκBα degradation, p38 MAPK phosphorylation and NF-κB dependent reporter activation induced by stimulants of TLR2 and TLR4 (Pam3CSK4 and LPS), but not by stimulants of other TLRs (PolyI:C, Flagellin, Loxoribine, ssRNA or CpG DNA) in macrophages and HEK-293 cells transfected with respective TLRs, and significantly reduced inflammatory responses in mice injected subcutaneously or intraperitoneally with Pam<sub>3</sub>CSK<sub>4</sub>. Serum proteins, including CD14 and LBP, were identified as key targets for the specificity of TLR-inhibition since supplementation with excess serum, or recombinant CD14 or LBP, reversed TLR2 inhibition by OxPAPC, while serum accessory proteins, or expression of membrane CD14, potentiated signalling via TLR2 and TLR4, but not other TLRs. Binding experiments and functional assays identified MD2 as a novel additional target of OxPAPC inhibition of LPS signalling. Synthetic Phospholipid oxidation products 1-palmitoyl-2-(5-oxovaleryl)-<i>sn</i>-glycero-3-phosphocholine and 1-palmitoyl-2-glutaryl-<i>sn</i>-glycero-3-phosphocholine inhibited TLR2-signalling from around ∼30μM. Taken together, these results suggest that Oxidised Phospholipid mediated inhibition of TLR-signalling occurs mainly by competitive interaction with accessory proteins that interact directly with bacterial lipids to promote signalling via TLR2 or TLR4
Griffiths H.r. - One of the best experts on this subject based on the ideXlab platform.
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Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients
'Elsevier BV', 2017Co-Authors: Ademowo O.s., Dias H.k.i., Devitt A., Moran R., Mulcahy R., Howard A.n., Nolan J.m., Griffiths H.r.Abstract:Alzheimer's disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD, therefore reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age-matched control subjects before and after carotenoid supplementation. The novel Oxidised Phospholipid biomarker 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) was analysed using electrospray ionization tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8-isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay. AD patients (n=21) and healthy age-matched control subjects (n=16) were supplemented with either Macushield™ (10 mg meso-zeaxanthin, 10 mg lutein, 2 mg zeaxanthin) or placebo (sunflower oil) for six months. The MRM-MS method determined serum POVPC sensitively (from 10 µl serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age-matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=−0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003). In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function
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Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients
'Elsevier BV', 2017Co-Authors: Ademowo O.s., Dias H.k.i., Devitt A., Moran R., Mulcahy R., Howard A.n., Nolan J.m., Griffiths H.r.Abstract:Alzheimer's disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD and reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age-matched control subjects before and after carotenoid supplementation. The novel Oxidised Phospholipid biomarker 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) was analysed using electrospray ionisation tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8-isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay. AD patients (n=21) and healthy age-matched control subjects (n=16) were supplemented with either Macushield™ (10 mg meso-zeaxanthin, 10 mg lutein, 2 mg zeaxanthin) or placebo (sunflower oil) for six months. The MRM-MS method determined serum POVPC sensitively (from 10 µl serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age-matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=−0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003). In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function.HRG and JMN gratefully acknowledge support from The Howard Foundation for this study. OSA was supported by the Aston Research Centre for Healthy Ageing. HKID gratefully acknowledges support from the Kidney ResearchFoundation PDF3/2014 and Alzheimer's Research UK network grantLES811839.IM, AD and HRG acknowledge support from the Biotechnology and Biological Sciences Research Council BB/M006298/
