Native LDL potentiate TNF alpha and IL-8 production by human mononuclear cells.

Abstract:

: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.

journal_name

J Lipid Res

authors

Netea MG,Kullberg BJ,Demacker PN,Jacobs LE,Verver-Jansen TJ,Hijmans A,van Tits LH,Hoenderop JG,Willems PH,Van der Meer JW,Stalenhoef AF

doi

10.1194/jlr.m100254-jlr200

keywords:

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

1065-71

issue

7

eissn

0022-2275

issn

1539-7262

journal_volume

43

pub_type

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