TRANSCRIPTION FACTOR NF-KAPPA-B AND INHIBITOR I-KAPPA-B-ALPHA ARE LOCALIZED IN MACROPHAGES IN ACTIVE MULTIPLE-SCLEROSIS LESIONS

NF-kappa B is a transcription factor family which on translocation to the nucleus regulates gene expression during cell activation. As such. NF-kappa B may play a role in the microglial response to myelin damag e in multiple sclerosis (MS) lesions. Here the cellular localization o f NF-kappa B and expression of the inhibitory I kappa B alpha were exa mined by immunocytochemistry on central nervous system (CNS) tissue fr om MS? and control cases. In normal control white matter, the active f orm of the NF-kappa B subunit RelA (p65) was localized in microglial n uclei, while the c-Rel and p50 subunits and the inhibitory I kappa B a lpha were restricted to the cytoplasm. In contrast, in actively demyel inating plaques, the RelA, c-Ret, and p50 subunits of NF-kappa B and I kappa B alpha were all present in macrophage nuclei in both parenchym al and perivascular areas. RelA was also found in the nuclei of a subs et of hypertrophic astrocytes. Only c-Rel had a nuclear localization i n lymphocytes in perivascular inflammatory cuffs. Our results suggest that constitutive activation of the RelA subunit in the nuclei of rest ing microglia may facilitate a rapid response to pathological stimuli in the CNS. Activation of the inducible NF-kappa B pool in macrophages in MS lesions could amplify the inflammatory reaction through upregul ation of NF-kappa B-controlled adhesion molecules and cytokines.