PMID- 8103050
OWN - NLM
STAT- MEDLINE
DCOM- 19930930
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 268
IP  - 25
DP  - 1993 Sep 5
TI  - Inhibition of interferon-gamma-induced major histocompatibility complex class II 
      gene transcription by interferon-beta and type beta 1 transforming growth factor 
      in human astrocytoma cells. Definition of cis-element.
PG  - 18794-800
AB  - To address mechanisms by which cytokines inhibit interferon-gamma (IFN 
      gamma)-induced gene expression in astrocytic cells, we have been studying effects 
      of type beta 1 transforming growth factor (TGF beta 1) and interferon-beta (IFN 
      beta) on IFN gamma-induced expression of the well-characterized human major 
      histocompatibility complex (MHC) class II gene DRA. This investigation was 
      motivated by the observations that IFN gamma-induced expression of MHC class II 
      antigen expression on astrocytic cells can be blocked in a tissue-specific 
      fashion by several cytokines and neurotransmitters in tissue culture and that 
      astrocyte expression of MHC class II is severely restricted in vivo. We 
      previously showed that IFN beta inhibited IFN gamma-induced DRA expression at the 
      transcriptional level. This inhibition was not global, since IFN gamma-induction 
      of intercellular adhesion molecule-1 was not affected. Here, TGF beta 1-mediated 
      inhibition of DRA is shown to exhibit similar characteristics. To address the 
      mechanism of this inhibition, sequence requirements for IFN beta and TGF beta 1 
      to suppress IFN gamma-induced transcription of DRA were determined. A 135-base 
      pair DRA sequence element containing the IFN gamma-responsive region and 
      transcriptional start site was sufficient to direct IFN beta- or TGF beta 
      1-mediated suppression of a reporter gene. These experiments suggested that 
      either IFN beta or TGF beta 1 could repress IFN gamma-induced DRA transcription 
      directly, without requiring a cis-element extrinsic to the IFN gamma-inducible 
      DRA sequences. Consistently similar effects of IFN beta and TGF beta 1 observed 
      in these experiments prompted comparison of other gene regulatory effects of the 
      two cytokines. TGF beta 1, unlike IFN beta, induced gene expression directed by 
      upstream elements of the gene encoding plasminogen activator inhibitor type-1. 
      IFN beta, unlike TGF beta 1, enhanced levels of 2'-5'-oligoadenylate synthetase 
      activity. Additionally, direct assay of TGF beta 1 and monoclonal anti-TGF beta 
      antibody blocking experiments were used to determine that cells treated with IFN 
      beta did not produce increased amounts of active or latent TGF beta. These data 
      argued that IFN beta and TGF beta 1 utilized distinct pathways to mediate the 
      inhibition of IFN gamma-induced DRA transcription.
FAU - Devajyothi, C
AU  - Devajyothi C
AD  - Research Institute, Cleveland Clinic Foundation, Ohio 44195.
FAU - Kalvakolanu, I
AU  - Kalvakolanu I
FAU - Babcock, G T
AU  - Babcock GT
FAU - Vasavada, H A
AU  - Vasavada HA
FAU - Howe, P H
AU  - Howe PH
FAU - Ransohoff, R M
AU  - Ransohoff RM
LA  - eng
GR  - NS-KO8-01265/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Transforming Growth Factor beta)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 77238-31-4 (Interferon-beta)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
RN  - EC 2.7.7.84 (2',5'-Oligoadenylate Synthetase)
SB  - IM
GS  - DRA
MH  - 2',5'-Oligoadenylate Synthetase/metabolism
MH  - Astrocytoma/*metabolism
MH  - Cell Adhesion Molecules/genetics
MH  - Chloramphenicol O-Acetyltransferase/genetics
MH  - Gene Expression
MH  - Genes, MHC Class II/*genetics
MH  - HLA-DR Antigens/genetics
MH  - Humans
MH  - Intercellular Adhesion Molecule-1
MH  - Interferon-beta/*pharmacology
MH  - Interferon-gamma/*pharmacology
MH  - *Transcription, Genetic
MH  - Transfection
MH  - Transforming Growth Factor beta/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 1993/09/05 00:00
MHDA- 1993/09/05 00:01
CRDT- 1993/09/05 00:00
PHST- 1993/09/05 00:00 [pubmed]
PHST- 1993/09/05 00:01 [medline]
PHST- 1993/09/05 00:00 [entrez]
AID - S0021-9258(17)46698-1 [pii]
PST - ppublish
SO  - J Biol Chem. 1993 Sep 5;268(25):18794-800.