Activation of nuclear factor-kB in the spinal cord of experimental allergic encephalomyelitis

The DNA-binding activity of nuclear factor (NF-kB) was found to be induced in the spinal cord of rats with experimental allergic encephalomyelitis (EA E), an animal model of multiple sclerosis (MS), from the onset of the disea se. This activation of NF-kB persisted throughout the disease period and de creased thereafter in the recovery phase. Supershift analysis of NF-kB DNA- binding activity in nuclear extracts of spinal cords showed that RelA/p65 a nd p50 subunits but not c-Rel/p75, RelB/p68 and p52 subunits were involved in DNA binding. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kB a ctivation, markedly inhibited the in vivo activation of NF-kB in the spinal cord of EAE rats and attenuated the clinical symptoms of EAE. These studie s suggest that activation of NF-kB plays an important role in the pathogene sis of EAE and inhibitors of NF-kB activation may have therapeutic importan ce in MS. (C) 2000 Published by Elsevier Science Ireland Ltd.