Native LDL potentiate TNF alpha and IL-8 production by human mononuclear cells.
SourceJournal of Lipid Research, 43, 7, (2002), pp. 1065-1071
Article / Letter to editor
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Journal of Lipid Research
SubjectThe role of cytokines in the pathophysiology of febrile illnesses and in host defense against infections; Lipoproteins and atherosclerose; Regulation of salt and water reabsorption in the renal collecting duct; Signal Transduction and Ion Transport; De rol van cytokinen in de pathofysiologie van koortsende ziekten en in de afweer tegen infecties; Lipoproteïnen en atherosclerose; Regulatie water en zouttransport in de verzamelbuis van de nier; Signaaltransductie en ionentransport
Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca(2+) mobilization. Ca(2+) mobilization is also involved in the induction of proinflammatory cytokines, important mediators involved in atherogenesis. The aim of the study was to evaluate the capacity of nLDL to affect spontaneous and lipopolysaccharide (LPS)-stimulated cytokine production. Preincubation of human peripheral blood mononuclear cells (PBMC) with nLDL for 24 h did not influence spontaneous production of tumor necrosis factor alpha (TNF alpha) or interleukin-8 (IL-8), but significantly potentiated LPS-induced production of these cytokines. nLDL preincubation of PBMC did not increase the expression of the LPS receptors Toll-like receptor-4, CD14, or CD11c/CD18. Potentiation of cytokine production by nLDL was mediated through induction of Ca(2+) mobilization, because: a) nLDL induced a sustained pattern of repetitive Ca(2+) transients in human PBMC; b) the Ca(2+) chelator fura 2-acetoxymethyl ester, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, an intracellular Ca(2+) chelator, inhibited the potentiating effect of nLDL on LPS-induced cytokine synthesis; c) induction of Ca(2+) mobilization by thapsigargin potentiated LPS-induced cytokine production. nLDL are able to potentiate LPS-induced production of cytokines by human PBMC, and this effect is probably mediated through induction of Ca(2+) mobilization. This may represent an important pathogenetic mechanism in atherogenesis induced by hyperlipoproteinemia.
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