Tumor necrosis factor-alpha and alphaB-crystallin up-regulation during antibody-mediated demyelination in vitro: a putative protective mechanism in oligodendrocytes.
By using an in vitro model of antibody-mediated demyelination, we investigated the relationship between tumor necrosis factor-alpha (TNF-alpha) and heat shock protein (HSP) induction with respect to oligodendrocyte survival. Differentiated aggregate cultures of rat telencephalon were subjected to demyelination by exposure to antibodies against myelin oligodendrocyte glycoprotein (MOG) and complement. Cultures were analyzed 48 hr after exposure. Myelin basic protein (MBP) expression was greatly decreased, but no evidence was found for either necrosis or apoptosis. TNF-alpha was significantly up-regulated. It was localized predominantly in neurons and to a lesser extent in astrocytes and oligodendrocytes, and it was not detectable in microglial cells. Among the different HSPs examined, HSP32 and alphaB-crystallin were up-regulated; they may confer protection from oxidative stress and from apoptotic death, respectively. These results suggest that TNF-alpha, often regarded as a promoter of oligodendroglial death, could alternatively mediate a protective pathway through alphaB-crystallin up-regulation.
Neurochemistry Laboratory, Department of Pediatrics, CHUV, Lausanne, Switzerland.
Cécile Besson
CB
Duvanel
Florianne
F
Monnet-Tschudi
Olivier
O
Braissant
Jean-Marie
JM
Matthieu
Paul
P
Honegger
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000009:adverse effects*; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000009:adverse effects; D003459:Crystallins / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009336:Necrosis / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects*; D051381:Rats; D013687:Telencephalon / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D000906:Antibodies; D003459:Crystallins; D005904:Glial Fibrillary Acidic Protein; C571328:Mog protein, rat; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases