Role of endocytosis in the transactivation of nuclear factor-κB by oxidized low-density lipoprotein

Oxidized low-density lipoprotein (oxLDL) has been shown to modulate transactivation by the peroxisome proliferator-activated receptor (PPAR)-gamma and by nuclear factor-kappa B (NF-kappa B). In the present study, the oxLDL signalling pathways involved in NF-kappa B transactivation were investigated by utilizing a reporter construct driven by three upstream NF-kappa B binding sites, and Various pharmacological inhibitors. OxLDL and its constituent lysophophatidylcholine (lysoPC) induced a rapid and transient increase in intracellular calcium and stimulated NF-kappa B transactivation in resting RAW264.7 macrophage cells in an oxidation-dependent manner. NF-kappa B activation by oxLDL or lysoPC was inhibited by inhibitors of protein kinase C or by a chelator of intracellular calcium. Tyrosine kinase or phosphatidylinositol 3-kinase inhibitors did not block NF-kappa B transactivation.