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.
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:Humanastrocytoma 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.
Authors: R Ostan; L Bucci; M Capri; S Salvioli; M Scurti; E Pini; D Monti; C Franceschi Journal: Neuroimmunomodulation Date: 2008-11-26 Impact factor: 2.492
Authors: R M Lawn; N W Boonmark; K Schwartz; G E Lindahl; D P Wade; C D Byrne; K J Fong; K Meer; L Patthy Journal: J Biol Chem Date: 1995-10-13 Impact factor: 5.157