Gene expression in cultured astrocytes
http://www.neurology.org/cgi/content/abstract/57/4/681
Neurology 2001;57:681-685
Jun-ichi Satoh, MD, PhD; and Yasuo
Kuroda, MD, PhD
Address correspondence and reprint
requests to Dr. Jun-ichi Satoh, Division of Neurology, Department of Internal
Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan; e-mail:
satoj1@post.saga-med.ac.jp
Background:
Recent clinical trials indicate that
interferon-ß (IFNß) is effective in reducing exacerbations
in relapsing–remitting MS, whereas IFNg
provokes acute relapses. However, the molecular mechanisms underlying the
beneficial effects of IFNß and the detrimental effects of IFNg
in MS remain to be characterized. Previously, the authors showed that IFNß
inhibited IFNg-induced
major histocompatibility complex (MHC) class II expression on astrocytes.
Objective:
To clarify the gene expression profile
in cultured fetal human astrocytes after exposure to IFNß, IFNg,
or IFNß plus IFNg.
Methods:
Astrocytes were incubated for 24
hours in the culture medium with or without inclusion of 50 ng/mL recombinant
human IFNß, IFNg,
or both. The gene expression profile was studied by analyzing a cDNA expression
array containing clones of various functional classes.
Results:
Among 1,185 clones examined, the
expression of six distinct genes was markedly induced after IFN treatment.
Northern blot analysis verified a significant up-regulation of mRNA for
interferon regulatory factor-7 (IRF-7) and pleiotrophin predominantly in
astrocytes treated with IFNß, both IRF-1 and intercellular adhesion
molecule-1 mRNA mainly in astrocytes treated with IFN, and signal transducer
and activator of transcription-1a
and MHC class I HLA-C mRNA equally in astrocytes exposed to either type
of IFN. In contrast, the treatment of astrocytes with either IFNß
or IFNg did not
alter the levels of expression of mRNA for brain-derived neurotrophic factor,
27-kd heat shock protein, prion protein, or defender against apoptotic
cell death-1. No antagonistic action was observed between IFNß and
IFNg in the pattern
of gene induction in astrocytes.
Conclusion:
A preferential induction of IRF-7
in IFNß-treated astrocytes and a predominant expression of IRF-1
in IFNg-exposed
astrocytes might contribute to one of the molecular mechanisms underlying
the clinically opposite effects of IFNß and IFNg
in MS.
© 2001 American Academy of Neurology
From the Division of Neurology,
Department of Internal Medicine, Saga Medical School, Japan.