[The role of activation of nuclear factor-kappa B of rat brain in the pathogenesis of experimental allergic encephalomyelitis].
To investigate the role of activated nuclear factor-kappaB (NF-kappaB) in experimental allergic encephalomyelitis (EAE), the activity and protein expression of NF-kappaB p65 in rat brain tissues, which were extracted from EAE rats at 1, 7, 14 and 21 d respectively after EAE was induced by CFA-GPSCH, were measured with electrophoretic mobility shift assay and immunohistochemistry. The relationship between activated NF-kappaB and symptoms of EAE was also investigated. The results showed that protein expression level and the activity of NF-kappaB were very low in the brain of the control group. After EAE was induced, the activity of NF-kappaB and the level of the protein expression in the brains increased gradually with the development of symptoms and brain pathology of EAE. On d 14, both the activity and the level of protein expression in the brains reached a peak, the positive cells of NF-kappaB were mainly located at the choroid plexuses and subfornical organ, as well as around the regions of   sleeve-like   lesion foci, which were coincident with the locations of lesions of EAE. The incidence, symptoms, reduction of the body weight and pathology of EAE rats brains at the above locations were most significant. On d 21 the activity of NF-kappaB and level of the protein expression reduced gradually, which was in parallel with a gradual alleviation of the symptoms of EAE rats. After a specific inhibitor of NF-kappaB, PDTC was applied, the symptoms and pathological lesions of EAE rat brain were mitigated markedly. The above results indicate that the dynamic changes in the activity and protein expression of NF-kappaB were in parallel with the changes in symptoms and pathological lesion of EAE rat brains. In conclusion, the activated NF-kappaB in the brain may play a critical role in the pathogenesis of EAE, and application of some inhibitors of NF-kappaB, such as PDTC, may be one of the effective therapeutic methods for prevention and treatment of EAE.
Tan
Guo-Jun
GJ
Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017. ttangjun@hotmail.com
Yang
Tian-Zhu
TZ
Zhao
Xiao-Yun
XY
Zhou
Li-Xia
LX
Cao
Cui-Li
CL
Ma
Chang-Sheng
CS
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D005260:Female; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013859:Thiocarbamates / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism*
D011759:Pyrrolidines; C498145:Rela protein, rat; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C020972:pyrrolidine dithiocarbamic acid