Activation of NF-kappa B and c-jun transcription factors in multiple sclerosis lesions - Implications for oligodendrocyte pathology

Citation
B. Bonetti et al., Activation of NF-kappa B and c-jun transcription factors in multiple sclerosis lesions - Implications for oligodendrocyte pathology, AM J PATH, 155(5), 1999, pp. 1433-1438
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
AMERICAN JOURNAL OF PATHOLOGY
ISSN journal
0002-9440 → ACNP
Volume
155
Issue
5
Year of publication
1999
Pages
1433 - 1438
Database
ISI
SICI code
0002-9440(199911)155:5<1433:AONBAC>2.0.ZU;2-#
Abstract
Oligodendrocytes are a major target of the purported autoimmune response in multiple sclerosis (MS) lesions, but little is known about the mechanisms underlying their demise. Despite the expression of pro-apoptotic receptors, these cells are rarely seen to undergo apoptosis in situ, On the other han d, cytotoxic mediators present in MS lesions, such as tumor necrosis factor -alpha, are known to generate survival signals through the activation of th e transcription factors NF-kappa B and c-jun, The aim of this study was to investigate in chronic active and silent MS lesions and control white matte r the expression of c-jun, its activating molecule, JNK, as well as NF-kapp a B complex and its inhibitor, I kappa B, By immunohistochemistry we found negligible reactivity for these molecules in control white matter and silen t MS plaques. In active MS lesions, double-label immunohistochemistry with oligodendrocyte markers showed up-regulation of the nuclear staining for bo th NF-kappa B and JNK on a large proportion of oligodendrocytes located at the edge of active lesions and on microglia/macrophages throughout plaques. Oligodendrocytes showed no reactivity for I kappa B, which was predominant ly confined to the cytoplasm of microglia/macrophages. We hypothesize that activation of these transcriptional pathways may be one mechanism accountin g for the paucity of oligodendrocyte apoptosis reported in MS.