Suppression of microglial inflammatory activity by myelin phagocytosis: role of reactive oxygen species generation via p47-PHOX

Multiple sclerosis (MS) is pathologically characterized by inflammatory demyelination and neuronal injury. Although phagocytosis of myelin debris by microglia and macrophages in acute MS lesion sites is well documented, its pathophysiological significance is unclear. Using real-time quantitative PCR, flow cytometry, ELISA and reactive oxygen species (ROS) measurement assays, we demonstrated that myelin phagocytosis in IFN-gamma-activated microglia down-regulates gene transcription of proinflammatory cytokines (particularly IL-1beta, the chemokine IP-10, and innate immune Toll-like receptors 1, 2, 9 and CD14. In…