NF-{kappa}B Activation Protects Oligodendrocytes against Inflammation

NF-B is a key player in inflammatory diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the effects of NF-B activation on oligodendrocytes in MS and EAE remain unknown. We generated a mouse model that expresses IBαN, a super-suppressor of NF-B, specifically in oligodendrocytes and demonstrated that IBαN expression had no effect on oligodendrocytes under normal conditions (both sexes). Interestingly, we showed that oligodendrocyte-specific expression of IBαN blocked NF-B activation in oligodendrocytes and resulted in exacerbated oligodendrocyte death and hypomyelination in young, developing mice that express IFN- ectopically in the CNS (both sexes). We also showed that NF-B inactivation in oligodendrocytes aggravated IFN--induced remyelinating oligodendrocyte death and remyelination failure in the cuprizone model (male mice). Moreover, we found that NF-B inactivation in oligodendrocytes increased the susceptibility of mice to EAE (female mice). These findings imply the cytoprotective effects of NF-B activation on oligodendrocytes in MS and EAE.

SIGNIFICANCE STATEMENT Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. NF-B is a major player in inflammatory diseases that acts by regulating inflammation and cell viability. Data indicate that NF-B activation in inflammatory cells facilitates the development of MS. However, to date, attempts to understand the role of NF-B activation in oligodendrocytes in MS have been unsuccessful. Herein, we generated a mouse model that allows for inactivation of NF-B specifically in oligodendrocytes and then used this model to determine the precise role of NF-B activation in oligodendrocytes in models of MS. The results presented in this study represent the first demonstration that NF-B activation acts cell autonomously to protect oligodendrocytes against inflammation in animal models of MS.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2xeFc0o