Induction of cytolysin mRNA in glial cells by IFN-gamma: a possible cytotoxic pathway in the CNS.
We utilized in situ hybridization to detect expression and regulation of cytolysin mRNA in microglia, astrocytes and oligodendrocytes from newborn rat brains. Expression under natural culture conditions was undetectable or very low, even after 10 days of culture. Cytolysin mRNA expression in microglia, astrocytes and oligodendrocytes was up-regulated by IFN-gamma. This up-regulation in glial cells was slow, and characterized by a gradually increased expression until day 10 of culture. IFN-gamma-mediated up-regulation of cytolysin mRNA was markedly more prominent in oligodendrocytes than in microglia and astrocytes. Unexpectedly, a combination of LPS and IFN-gamma did not exhibit a synergistic effect in the induction of cytolysin mRNA expression in the three types of glial cells. On the contrary, LPS strongly inhibited IFN-gamma-mediated cytolysin mRNA expression in microglia, astrocytes and oligodendrocytes. These results reveal that there may exist a glial cell-dependent cytotoxic pathway within the CNS, and that inducible cytolysin may play an important role in destruction of oligodendrocytes or clearance of infiltrating cells within the CNS in inflammatory diseases such as multiple sclerosis or experimental allergic encephalomyelitis.
Xiao
B G
BG
Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
Bao
W J
WJ
Bai
X F
XF
Link
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H
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002490:Central Nervous System / Q000166:cytology* / Q000187:drug effects; D003603:Cytotoxins / Q000096:biosynthesis*; D004731:Endotoxins / Q000494:pharmacology; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011994:Recombinant Proteins
D003603:Cytotoxins; D004731:Endotoxins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C044101:endotoxin, Escherichia coli; D007371:Interferon-gamma