Poster Sessions BP05: Neuroimmunology. Inhibition of adoptive transfer of EAE by nemo‐binding domain (NBD) peptides

Abstract

Experimental allergic encephalomyelitis (EAE) is the animal model for Multiple Sclerosis (MS), the chronic autoimmune disease of the central nervous system (CNS). Activation of NF‐κB requires the activity of IkB kinase (IKK) complex containing (IKKa and IKKb) and the regulatory protein NEMO (NF‐κB essential modifier). Recently it has been shown that peptides corresponding to the NEMO‐binding domain (NBD) of IKKa or IKKb specifically inhibit the induction of NF‐κB activation without inhibiting the basal NF‐κB activity. The present study underlines the importance of cell‐permeable NBD peptides in inhibiting the disease process of adoptively‐transferred EAE in female SJL/J mice. Immunocytochemical analysis of spinal cords of EAE mice showed that there was marked induction of NF‐κB activation as evidenced by enhanced p65 (the RelA subunit of NF‐κB) expression compared to that of control mice. Double‐labelling analysis of p65 and cell‐specific markers showed that p65 was mainly expressed by astrocytes, microglia and infiltrating macrophages. Next we examined the effect of NBD peptides on the disease process of EAE. Interestingly, clinical symptoms of EAE were much lower in mice receiving wild type NBD peptides. In contrast, mutated NBD peptides had no effect on the clinical symptoms of EAE. Taken together, our results support the conclusion that activation of NF‐κB participates in the disease process of EAE and that inhibitors of NF‐κB activation may ameliorate the neuroinflammatory disease process in MS patients.Acknowledgements: This study was supported by NIH grants (NS39940 and AG19487.