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


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.
Department of Biochemistry and Molecular Biology, "Ernesto Quagliariello", University of Bari, Via Orabona 4, 70126, Bari, Italy.
Guglielmina
G
Chimienti
Anna
A
Mezzapesa
Grazia M
GM
Liuzzi
Tiziana
T
Latronico
Gabriella
G
Pepe
D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism*; D001254:Astrocytoma / Q000378:metabolism* / Q000503:physiopathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D001054:Apolipoproteins A; D015850:Interleukin-6; D008070:Lipopolysaccharides