The role of liver X receptors in the macrophage response after myelin phagocytosis

Abstract

Classically, macrophages are hypothesized to be only detrimental in MS. However, recent evidence suggests that macrophages may also be protective. Nonetheless, underlying mechanisms remain to be clarified. One such possible mechanism is the activation of LXRs. Interestingly, myelin contains cholesterol and LXRs are activated by cholesterol derivatives. We hypothesized that LXRs are activated by myelin phagocytosis and induce a protective phenotype in macrophages. First, the activation of LXR response genes, after myelin phagocytosis, was investigated in macrophages by RT-PCR. Next, macrophage production of inflammatory mediators, after myelin phagocytosis and LXR activation, was investigated. We demonstrated that LXRs are activated after myelin phagocytosis and that multiple mechanisms, probably including LXR signalling, are involved in inducing a protective phenotype in macrophages after myelin phagocytosis.