The purpose of the present study was to investigate the ability of high-density lipoproteins (HDL) to attenuate endothelial dysfunction, by assessing down-regulation of cytokine-induced interleukin-6 (IL-6) production in cultured endothelial cells, and measuring plasma IL-6 levels in three groups of healthy individuals with low, average, or high plasma HDL-cholesterol. Human plasma HDL caused a concentration-dependent inhibition of TNFα-induced IL-6 production in human endothelial cells (by 58.5 ± 1.5% at 2 mg of HDL-protein/ml). Reconstituted HDL made with apolipoprotein A-I (apoA-I) and phosphatidylcholine were as effective as plasma HDL, while lipid-free apoA-I or phosphatidylcholine liposomes had no effect. HDL attenuated IL-6 mRNA levels, an effect which occurs through inhibition of p38 MAP kinase. The median plasma IL-6 concentration was significantly higher in subjects with low HDL-cholesterol (2.54 pg/ml) compared with those with average or high HDL-cholesterol (1.31 pg/ml and 1.47 pg/ml, respectively). When all subjects were considered together, a lower HDL-cholesterol was the strongest independent predictor of higher IL-6 (F = 25.38, P < 0.001). By inhibiting IL-6 production and lowering plasma IL-6 concentration, HDL may limit the pro-atherogenic effects of both acute and chronic inflammatory states, of which IL-6 is a key orchestrator.
High-density lipoproteins attenuate interleukin-6 production in endothelial cells exposed to pro-inflammatory stimuli / M. Gomaraschi, N. Basilico, F. Sisto, D. Taramelli, S. Eligini, S. Colli, C. Sirtori, G. Franceschini, L. Calabresi. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS. - ISSN 1388-1981. - 1736:2(2005), pp. 136-143.
High-density lipoproteins attenuate interleukin-6 production in endothelial cells exposed to pro-inflammatory stimuli
M. GomaraschiPrimo
;N. BasilicoSecondo
;F. Sisto;D. Taramelli;S. Eligini;S. Colli;C. Sirtori;G. FranceschiniPenultimo
;L. CalabresiUltimo
2005
Abstract
The purpose of the present study was to investigate the ability of high-density lipoproteins (HDL) to attenuate endothelial dysfunction, by assessing down-regulation of cytokine-induced interleukin-6 (IL-6) production in cultured endothelial cells, and measuring plasma IL-6 levels in three groups of healthy individuals with low, average, or high plasma HDL-cholesterol. Human plasma HDL caused a concentration-dependent inhibition of TNFα-induced IL-6 production in human endothelial cells (by 58.5 ± 1.5% at 2 mg of HDL-protein/ml). Reconstituted HDL made with apolipoprotein A-I (apoA-I) and phosphatidylcholine were as effective as plasma HDL, while lipid-free apoA-I or phosphatidylcholine liposomes had no effect. HDL attenuated IL-6 mRNA levels, an effect which occurs through inhibition of p38 MAP kinase. The median plasma IL-6 concentration was significantly higher in subjects with low HDL-cholesterol (2.54 pg/ml) compared with those with average or high HDL-cholesterol (1.31 pg/ml and 1.47 pg/ml, respectively). When all subjects were considered together, a lower HDL-cholesterol was the strongest independent predictor of higher IL-6 (F = 25.38, P < 0.001). By inhibiting IL-6 production and lowering plasma IL-6 concentration, HDL may limit the pro-atherogenic effects of both acute and chronic inflammatory states, of which IL-6 is a key orchestrator.Pubblicazioni consigliate
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