title: Constitutive NF-kappa B activity in neurons.
abstract: NF-kappa B is inducible transcription factor present in many cell types in a latent cytoplasmic form. So far, only immune cells including mature B cells, thymocytes, and adherent macrophages have been reported to contain constitutively active forms of NF-kappa B in the nucleus. A recent study showed that the human immunodeficiency virus type 1 (HIV-1) promoter is highly active in several brain regions of transgenic mice (J. R. Corboy, J. M. Buzy, M. C. Zink, and J. E. Clements, Science 258:1804-1807, 1992). Since the activity of this viral enhancer is governed mainly by two binding sites for NF-kappa B, we were prompted to investigate the state of NF-kappa B activity in neurons. Primary neuronal cultures derived from rat hippocampus and cerebral cortex showed a high constitutive expression of an HIV-1 long terminal repeat-driven luciferase reporter gene, which was primarily dependent on intact NF-kappa B binding sites and was abolished upon coexpression of the NF-kappa B-specific inhibitor I kappa B-alpha. Indirect immunofluorescence and confocal laser microscopy showed that the activity of NF-kappa B correlated with the presence of the NF-kappa B subunits p50 and RelA (p65) in nuclei of cultured neurons. NF-kappa B was also constitutively active in neurons in vivo. As investigated by electrophoretic mobility shift assays, constitutive NF-kappa B DNA-binding activity was highly enriched in fractions containing neuronal nuclei prepared from rat cerebral cortex. Nuclear NF-kappa B-specific immunostaining was also seen in cryosections from mouse cerebral cortex and hippocampus. Only a subset of neurons was stained. Activated NF-kappa B in the brain is likely to participate in normal brain function and to reflect a distinct state of neuronal activity or differentiation. Furthermore, it may explain the high level of activity of the HIV-1 enhancer in neurons, an observation potentially relevant for the etiology of the AIDS dementia complex caused by HIV infection of the central nervous system.
authors.affiliation: Institute of Biochemistry, Albert-Ludwigs-Universität, Freiburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kaltschmidt
authors.forename: B
authors.initials: B
authors.lastname: Kaltschmidt
authors.forename: H
authors.initials: H
authors.lastname: Neumann
authors.forename: H
authors.initials: H
authors.lastname: Wekerle
authors.forename: P A
authors.initials: PA
authors.lastname: Baeuerle
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics; D006367:HeLa Cells; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000378:metabolism; D016328:NF-kappa B / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D016328:NF-kappa B; D051996:Transcription Factor RelA; D008156:Luciferases