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标题：Native LDL potentiate TNFα and IL-8 production by human mononuclear cells
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作者：Mihai G. Netea ; Bart Jan Kullberg ; Pierre N. M. Demacker 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2002
卷号：43
期号：7
页码：1065-1071
DOI：10.1194/jlr.M100254-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca²⁺ mobilization. Ca²⁺ 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 α (TNFα) 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 Ca²⁺ mobilization, because: a ) nLDL induced a sustained pattern of repetitive Ca²⁺ transients in human PBMC; b ) the Ca²⁺ chelator fura 2-acetoxymethyl ester, 1,2-bis(2-aminophenoxy)ethane- N , N , N ′, N ′-tetraacetic acid, an intracellular Ca²⁺ chelator, inhibited the potentiating effect of nLDL on LPS-induced cytokine synthesis; c ) induction of Ca²⁺ 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 Ca²⁺ mobilization. This may represent an important pathogenetic mechanism in atherogenesis induced by hyperlipoproteinemia.