High-density lipoproteins attenuate interleukin-6 production in endothelial cells exposed to pro-inflammatory stimuli

Monica Gomaraschi, Nicoletta Basilico, Francesca Sisto, Donatella Taramelli, Sonia Eligini, Susanna Colli, Cesare R. Sirtori, Guido Franceschini, Laura Calabresi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)136-143
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1736
Issue number2
DOIs
Publication statusPublished - Sep 15 2005

Keywords

  • Atherosclerosis
  • Endothelial function
  • High-density lipoprotein
  • Interleukin

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics

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