Transcription factor NF-kappaB and inhibitor I kappaBalpha are localized in macrophages in active multiple sclerosis lesions.
NF-kappaB is a transcription factor family which on translocation to the nucleus regulates gene expression during cell activation. As such, NF-kappaB may play a role in the microglial response to myelin damage in multiple sclerosis (MS) lesions. Here the cellular localization of NF-kappaB and expression of the inhibitory I kappaBalpha 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-kappaB subunit RelA (p65) was localized in microglial nuclei, while the c-Rel and p50 subunits and the inhibitory I kappaBalpha were restricted to the cytoplasm. In contrast, in actively demyelinating plaques, the RelA, c-Rel, and p50 subunits of NF-kappaB and I kappaBalpha 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-kappaB pool in macrophages in MS lesions could amplify the inflammatory reaction through upregulation of NF-kappaB-controlled adhesion molecules and cytokines.
Gveric
D
D
Multiple Sclerosis Laboratory, Institute of Neurology, London, England.
Kaltschmidt
C
C
Cuzner
M L
ML
Newcombe
J
J
D000328:Adult; D000368:Aged; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology; D002467:Cell Nucleus / Q000473:pathology / Q000648:ultrastructure; D002544:Cerebral Infarction / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis*; D003711:Demyelinating Diseases / Q000473:pathology; D006801:Humans; D020672:I-kappa B Proteins; D007150:Immunohistochemistry; D007249:Inflammation; D008264:Macrophages / Q000473:pathology*; D017628:Microglia / Q000166:cytology / Q000473:pathology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000032:analysis* / Q000037:antagonists & inhibitors; D010487:Periaqueductal Gray / Q000166:cytology / Q000276:immunology / Q000473:pathology; D012016:Reference Values; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha