Transcription factor NF-kappaB and inhibitor I kappaBalpha 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 damage in multiple sclerosis (MS) lesions. Here the cellular localization of NF-kappa B and expression of the inhibitory I kappa B alpha were examined by immunocytochemistry on central nervous system (CNS) tissue from MS? and control cases. In normal control white matter, the active form of the NF-kappa B subunit RelA (p65) was localized in microglial nuclei, while the c-Rel and p50 subunits and the inhibitory I kappa B alpha were restricted to the cytoplasm. In contrast, in actively demyelinating 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 parenchymal and perivascular areas. RelA was also found in the nuclei of a subset of hypertrophic astrocytes. Only c-Rel had a nuclear localization in lymphocytes in perivascular inflammatory cuffs. Our results suggest that constitutive activation of the RelA subunit in the nuclei of resting 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 upregulation of NF-kappa B-controlled adhesion molecules and cytokines.