Effects of Macrophages on Myogenicity of Dysferlin-Deficient Myoblasts
Dysferlin-deficient muscle is marked by inflammatory foci that contain infiltrating macrophages. Classically activated macrophages are involved in phagocytosis and removal of necrotic tissue whereas wound-healing macrophages are involved in repair and promotion of muscle regeneration. The aim of these studies is to define the effects of these two macrophage phenotypes on muscle cells. The approach uses an in vitro macrophage and myoblast co-culture system in which diffusible factors are exchanged. Using this approach, M1 macrophage-derived cytokine IL1beta was identified as a factor that inhibits muscle differentiation whereas M2 macrophage-derived cytokine IL-4 potentiates muscle differentiation. This approach will also determine whether pharmaceutical manipulation of macrophages is possible that would shift the balance towards promoting myogenesis and regeneration.