PMID- 10465294
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20081121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 140
IP  - 9
DP  - 1999 Sep
TI  - Tumor necrosis factor-alpha and interferon-gamma suppress both gene expression 
      and deoxyribonucleic acid-binding of TTF-2 in FRTL-5 cells.
PG  - 4214-20
AB  - Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are 
      cytokines that can individually or additively suppress thyroid cell function and 
      the expression of thyroid-specific genes, such as thyroglobulin (TG) and 
      thyroperoxidase (TPO). Thyroid transcription factor-2 (TTF-2) is a DNA-binding 
      protein that modulates the expression of TG and TPO genes. In the present study, 
      we examine the effects of TNF-alpha and IFN-gamma on TTF-2 gene expression, as 
      well as the DNA-binding activity of TTF-2. FRTL-5 cells were maintained in 5H 
      medium containing 0.2% calf serum for 7 days, then incubated with TNF-alpha, 
      IFN-gamma, or TNF-alpha plus IFN-gamma. Total RNA was isolated and Northern 
      blotted. TNF-alpha (50 ng/ml) only slightly suppressed (61+/-2% compared with 
      control), whereas IFN-gamma (100 U/ml) modestly decreased TTF-2 messenger RNA 
      (mRNA) levels (34+/-4%). TNF-alpha and IFN-gamma simultaneously caused a marked 
      decrease in TTF-2 mRNA levels (13+/-2%). The suppressive effects of TNF-alpha and 
      IFN-gamma on TTF-2 mRNA levels were concentration dependent and maximal at 50 
      ng/ml TNF-alpha with 100 U/ml IFN-gamma. The suppressive effect was also time 
      dependent, reaching a maximum 12 h after exposure. Moreover, the suppressive 
      effects of TNF-alpha and IFN-gamma upon rat TG and TTF-2 mRNA levels were 
      similar. To test whether TNF-alpha and IFN-gamma alter TTF-2-binding to DNA, we 
      performed electrophoretic mobility shift assays using a TTF-2-binding element in 
      the rat TG gene as a probe. Formation of the TTF-2/DNA complex was decreased by 
      TNF-alpha and/or IFN-gamma. Our results demonstrate that TNF-alpha and IFN-gamma 
      additively reduce the gene expression and DNA-binding of TTF-2. These data 
      suggest that TTF-2 is involved in the TNF-alpha and IFN-gamma-induced suppression 
      of thyroid-specific gene expression.
FAU - Miyazaki, A
AU  - Miyazaki A
AD  - Third Department of Internal Medicine, Yamanashi Medical University, Tamaho, 
      Japan.
FAU - Shimura, H
AU  - Shimura H
FAU - Endo, T
AU  - Endo T
FAU - Haraguchi, K
AU  - Haraguchi K
FAU - Onaya, T
AU  - Onaya T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (FOXE1 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Repressor Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - DNA/*metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Forkhead Transcription Factors
MH  - Gene Expression/*drug effects
MH  - Interferon-gamma/*pharmacology
MH  - RNA, Messenger/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Repressor Proteins/genetics/*metabolism
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1999/08/28 00:00
MHDA- 1999/08/28 00:01
CRDT- 1999/08/28 00:00
PHST- 1999/08/28 00:00 [pubmed]
PHST- 1999/08/28 00:01 [medline]
PHST- 1999/08/28 00:00 [entrez]
AID - 10.1210/endo.140.9.6982 [doi]
PST - ppublish
SO  - Endocrinology. 1999 Sep;140(9):4214-20. doi: 10.1210/endo.140.9.6982.