Transcription factor NF-κB and inhibitor IκBα are localized in macrophages in active multiple sclerosis lesions

Abstract

NF-κB is a transcription factor family which on translocation to the nucleus regulates gene expression during cell activation. As such, NF-κB may play a role in the microglial response to myelin damage in multiple sclerosis (MS) lesions. Here the cellular localization of NF-κB and expression of the inhibitory IκBα 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-κB subunit RelA (p65) was localized in microglial nuclei, while the c-Rel and p50 subunits and the inhibitory IκBα were restricted to the cytoplasm. In contrast, in actively demyelinating plaques, the RelA, c-Rel, and p50 subunits of NF-κB and InBα 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-κB pool in macrophages in MS lesions could amplify the inflammatory reaction through upregulation of NF-κB-controlled adhesion molecules and cytokines.