Apolipoprotein E enhances nitric oxide production in Poly I:Poly C-treated RAW (264.7) cells

It has been reported that apolipoprotein E may be associated with the oxidative stress induced during chronic neurodegenerative diseases. We have previously reported that the polyribonucleotide, PolyI:C, enhances nitric oxide production in apoE treated human monocyte-derived macrophages. In an effort to further investigate the mechanism of nitric oxide production in response to apolipoprotein E stimulation, RAW (264.7) cells, a high-output NO cell line were used. We have found that nitrite production can be significantly enhanced by costimulation with physiological levels of apolipoprotein E. Priming of RAW cells with γIFN resulted in dose-dependent increase in nitrite production. γIFN-primed macrophages were treated with apoE in concentrations ranging from 1nM to 100nM for 24 hours and the conditioned media was assayed for nitrite production. Cells were also γIFN-primed and treated with 50 ng/ml Poly I:C and 1-100nM apolipoprotein E and assayed for nitrite production. Apolipoprotein E resulted in a two-fold increase in nitrite production, above Poly I:C treatment alone. The increase in nitrite was specific for nitric oxide synthase (NOS), since the NOS-inhibitor L-NMMA reduced nitrite levels to the levels seen in the untreated controls.

Duke Scholars

Author Carol Anne Colton Neurology, Behavioral Neurology