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 (EAE), an animal model of multiple sclerosis (MS), from the onset of the disease. This activation of NF-kB persisted throughout the disease period and decreased thereafter in the recovery phase. Supershift analysis of NF-kB DNA-binding activity in nuclear extracts of spinal cords showed that RelA/p65 and 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 activation, markedly inhibited the in vivo activation of NF-kB in the spinal cord of EAE rats and attenuated the clinical symptoms of EAE. These studies suggest that activation of NF-kB plays an important role in the pathogenesis of EAE and inhibitors of NF-kB activation may have therapeutic importance in MS.
Pahan
K
K
Department of Oral Biology, University of Nebraska Medical Center, Lincoln, 40th and Holdrege, Nebraska, NE 68583, USA. kpahan@unmc.edu
Schmid
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D013859:Thiocarbamates / Q000494:pharmacology
D000975:Antioxidants; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid