PMID- 10499522
OWN - NLM
STAT- MEDLINE
DCOM- 19991012
LR  - 20171116
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 140
IP  - 10
DP  - 1999 Oct
TI  - Tumor necrosis factor-alpha regulation of thyroid transcription factor-1 and 
      Pax-8 in rat thyroid FRTL-5 cells.
PG  - 4651-8
AB  - Tumor necrosis factor-alpha (TNF-alpha) is known to modulate the expression of 
      thyroid-specific genes, such as thyroglobulin (TG), contributing to the 
      pathogenesis of autoimmune thyroid disease. In the present study, we show that 
      TNF-alpha suppresses DNA-binding activity of thyroid transcription factors, Pax-8 
      and thyroid transcription factor-1 (TTF-1), which is, in part, involved in 
      TNF-alpha-induced decrease in TG gene expression. Transfected into rat thyroid 
      FRTL-5 cells, the activity of reporter plasmid containing the rat TG promoter 
      ligated to a luciferase gene was significantly suppressed in the presence of 
      TNF-alpha. In gel mobility shift analyses, protein-DNA complexes formed by TTF-1 
      and Pax-8 were reduced when the nuclear extracts prepared from TNF-alpha-treated 
      FRTL-5 cells were used. The suppressive effect of TNF-alpha on TTF-1-DNA complex 
      formation is, in part, caused by suppression of TTF-1 gene transcription by 
      TNF-alpha. Expressions of TTF-1 messenger RNA and protein, which were assessed by 
      Northern blot and Western blot analyses, respectively, were decreased by 
      TNF-alpha treatment of FRTL-5 cells. In contrast, TNF-alpha did not affect the 
      expression of Pax-8 messenger RNA. Treatment of FRTL-5 cells with TNF-alpha 
      caused a decrease in Pax-8 protein in nuclear extracts and accumulation of the 
      protein in the cytoplasm, as assessed by Western blot analyses. Mutation of the 
      TTF-1/Pax-8-binding site lost the TNF-alpha-induced decrease in TG promoter 
      activity in a transfection experiment. These results indicate that TNF-alpha 
      suppresses the activity of TTF-1 and Pax-8 by different mechanisms, which, in 
      part, seem to be involved in TNF-alpha-induced decrease in TG gene expression.
FAU - Ohmori, M
AU  - Ohmori M
AD  - Third Department of Internal Medicine, Yamanashi Medical University, Tamaho, 
      Japan.
FAU - Harii, N
AU  - Harii N
FAU - Endo, T
AU  - Endo T
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 (Nkx2-1 protein, rat)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PAX8 Transcription Factor)
RN  - 0 (Paired Box Transcription Factors)
RN  - 0 (Pax8 protein, rat)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thyroid Nuclear Factor 1)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-49-2 (DNA)
RN  - 9010-34-8 (Thyroglobulin)
SB  - IM
MH  - Animals
MH  - Base Sequence/genetics
MH  - Binding Sites/physiology
MH  - Cell Line
MH  - Cell Nucleus/drug effects/metabolism
MH  - Chimera/genetics
MH  - Cytoplasm/metabolism
MH  - DNA/metabolism
MH  - DNA-Binding Proteins/antagonists & inhibitors/genetics/*metabolism/physiology
MH  - Mutation/physiology
MH  - Nuclear Proteins/genetics/*metabolism/physiology
MH  - PAX8 Transcription Factor
MH  - Paired Box Transcription Factors
MH  - Promoter Regions, Genetic/drug effects/genetics/physiology
MH  - RNA, Messenger/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Thyroglobulin/genetics
MH  - Thyroid Gland/cytology/*metabolism
MH  - Thyroid Nuclear Factor 1
MH  - Trans-Activators/antagonists & inhibitors/genetics/*metabolism/physiology
MH  - Transcription Factors/genetics/*metabolism/physiology
MH  - Tumor Necrosis Factor-alpha/pharmacology/*physiology
EDAT- 1999/09/28 00:00
MHDA- 1999/09/28 00:01
CRDT- 1999/09/28 00:00
PHST- 1999/09/28 00:00 [pubmed]
PHST- 1999/09/28 00:01 [medline]
PHST- 1999/09/28 00:00 [entrez]
AID - 10.1210/endo.140.10.7021 [doi]
PST - ppublish
SO  - Endocrinology. 1999 Oct;140(10):4651-8. doi: 10.1210/endo.140.10.7021.