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
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
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.