Apolipoprotein(a) inhibits lipopolysaccharide-induced IL-6 secretion in human astrocytoma cell line by interfering with lipopolysaccharide signaling

Inflamm Res. 2011 Apr;60(4):329-35. doi: 10.1007/s00011-010-0272-7. Epub 2010 Nov 2.

Abstract

Objective: To examine the role of lipoprotein(a) [Lp(a)] on the inflammatory response of cells in the nervous system by investigating its effect on lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) secretion.

Materials and methods: Human astrocytoma U373 cells were treated with recombinant apolipoprotein(a) [r-apo(a)] A10K (175-11 nM), alone or in combination with LPS (100 and 10 ng/ml). IL-6 levels were evaluated by immunoblotting. Statistical analysis was performed by one-way ANOVA.

Results: r-apo(a) caused dose-dependent inhibition of LPS-induced IL-6 secretion (100 ng/ml LPS, p = 0.0205; 10 ng/ml LPS, p = 0.0005). Pre-treatment of cells with 88 nM r-apo(a), rinsing, and activation with 10 ng/ml LPS did not reverse the inhibition (p = 0.0048), which could be reversed by supplementation with excess serum (5-20%) (p = 0.0454) or recombinant CD14 (2.0-0.05 μg/ml) (p = 0.0230).

Conclusions: Our data indicate that apo(a) plays a natural anti-endotoxin role which relies on its interference with cell-associated and serum components of LPS signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins A / genetics
  • Apolipoproteins A / metabolism*
  • Astrocytoma / metabolism*
  • Astrocytoma / physiopathology*
  • Cell Line, Tumor / drug effects
  • Humans
  • Interleukin-6 / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Signal Transduction / drug effects*

Substances

  • Apolipoproteins A
  • Interleukin-6
  • Lipopolysaccharides