Myelin-Induced Inflammation And The Underlying Mechanism

Pro-inflammatory response following central nervous system (CNS) injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators. On the other hand, Myelin degeneration occurs after injury, which is identified as demyelination. Although lots of studies have focused on these two aspects, the direct relationship between them is still unclear during injury. We found that myelin debris have pro-inflammatory effect both in vivo and in ritro. Myelin injection into mouse peritoneal cavity and spinal cord can induce infiltration of immune cells (such as, neutrophils and macrophages) and increase the expression of pro-inflammatory mediators, such as IL-1?and TNF-a, which is in a complement receptor 3(CR3)-dependent manner. Moreover, myelin can up-regulate the expression of many pro-inflammatory cytokines and chemokines in mouse macrophages through CR3-FAK-PI3K-Akt-NFkB pathway. In conclusion, our results demonstrate a crucial role of myelin as an endogenous inflammatory stimulus that induces pro-inflammatory responses and suggest that blocking myelin-CR3 interaction and enhancing myelin debris clearance may be effective interventions for treating CNS injury.