PMID- 11524479
OWN - NLM
STAT- MEDLINE
DCOM- 20010927
LR  - 20190514
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 57
IP  - 4
DP  - 2001 Aug 28
TI  - Differing effects of IFN beta vs IFN gamma in MS: gene expression in cultured 
      astrocytes.
PG  - 681-5
AB  - BACKGROUND: Recent clinical trials indicate that interferon-beta (IFN beta) is 
      effective in reducing exacerbations in relapsing-remitting MS, whereas IFN gamma 
      provokes acute relapses. However, the molecular mechanisms underlying the 
      beneficial effects of IFN beta and the detrimental effects of IFN gamma in MS 
      remain to be characterized. Previously, the authors showed that IFN beta 
      inhibited IFN gamma-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 IFN beta, IFN gamma, or IFN 
      beta plus IFN gamma. METHODS: Astrocytes were incubated for 24 hours in the 
      culture medium with or without inclusion of 50 ng/mL recombinant human IFN beta, 
      IFN gamma, 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 IFN beta, both IRF-1 and intercellular adhesion 
      molecule-1 mRNA mainly in astrocytes treated with IFN gamma, and signal 
      transducer and activator of transcription-1 alpha and MHC class I HLA-C mRNA 
      equally in astrocytes exposed to either type of IFN. In contrast, the treatment 
      of astrocytes with either IFN beta or IFN gamma 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 IFN beta and IFN gamma in the pattern of 
      gene induction in astrocytes. CONCLUSION: A preferential induction of IRF-7 in 
      IFN beta-treated astrocytes and a predominant expression of IRF-1 in IFN 
      gamma-exposed astrocytes might contribute to one of the molecular mechanisms 
      underlying the clinically opposite effects of IFN beta and IFN gamma in MS.
FAU - Satoh, J
AU  - Satoh J
AD  - Division of Neurology, Department of Internal Medicine, Saga Medical School, 
      Nabeshima, Japan. satoj1@post.saga-med.ac.jp
FAU - Kuroda, Y
AU  - Kuroda Y
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (IRF1 protein, human)
RN  - 0 (IRF7 protein, human)
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (Interferon Regulatory Factor-7)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 77238-31-4 (Interferon-beta)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Astrocytes/*drug effects/*metabolism
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/metabolism
MH  - Fetus
MH  - Gene Expression/*drug effects/physiology
MH  - Humans
MH  - Interferon Regulatory Factor-1
MH  - Interferon Regulatory Factor-7
MH  - Interferon-beta/*pharmacology
MH  - Interferon-gamma/*pharmacology
MH  - Multiple Sclerosis/*metabolism
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Phosphoproteins/metabolism
MH  - RNA, Messenger/metabolism
EDAT- 2001/08/29 10:00
MHDA- 2001/09/28 10:01
CRDT- 2001/08/29 10:00
PHST- 2001/08/29 10:00 [pubmed]
PHST- 2001/09/28 10:01 [medline]
PHST- 2001/08/29 10:00 [entrez]
AID - 10.1212/wnl.57.4.681 [doi]
PST - ppublish
SO  - Neurology. 2001 Aug 28;57(4):681-5. doi: 10.1212/wnl.57.4.681.