PMID- 10404391
OWN - NLM
STAT- MEDLINE
DCOM- 19990830
LR  - 20081121
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 74
IP  - 2
DP  - 1999 Aug 1
TI  - Induction of transcription factor interferon regulatory factor-1 by 
      interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) in 
      FRTL-5 cells.
PG  - 211-9
AB  - While it is well known that interferon-gamma (IFN gamma) and tumor necrosis 
      factor-alpha (TNF alpha) play a role in the regulation of thyroid growth and 
      differentiated functions, the cellular and molecular mechanisms involved in 
      mediating the effects of IFN gamma and TNF alpha on thyroid function are unknown. 
      In the present study, we used FRTL-5 rat thyroid cells to examine the effects of 
      IFN gamma and TNF alpha on gene expression of transcription factor interferon 
      regulatory factor-1 (IRF-1), which is involved in mediating the effects of these 
      cytokines in a number of cell types. Northern blot analysis of FRTL-5 mRNA showed 
      a single IRF-1 mRNA at 2.2 Kb. In quiescent FRTL-5 cells, IRF-1 mRNA levels were 
      low but detectable by Northern analysis. Incubation of FRTL-5 cells with IFN 
      gamma or TNF alpha resulted in a dose- and time-dependent increase in IRF-1 mRNA 
      levels. We have shown that TNF-alpha and IFN-gamma act synergistically to block 
      the TSH-induced increase in type I 5'-deiodinase(5'D-I) activity and 5'D-I gene 
      expression in FRTL-5 rat thyroid cells. Incubation of FRTL-5 cells with IFN gamma 
      and TNF alpha in combination, however, did not synergistically increase IRF-1 
      mRNA levels. Electrophoretic mobility shift assay (EMSA) revealed that IFN gamma 
      induced the formation of a single complex to a IFN gamma activation site (GAS) 
      probe in a dose dependent manner. Several lines of evidence suggest that TNF 
      alpha activates transcription factor nuclear factor-kappa B (NF kappa B) through 
      activation of protein kinase C (PKC) or the hydrolysis of sphingomyelin to 
      ceramide in a number of cell types. Here we demonstrate that hydrolysis of 
      sphingomyelin to ceramide by sphingomyelinase (SMase), but not activation of PKC 
      by 12-O-tetradecanoylphorbol 13-acetate (TPA), was involved in the activation of 
      NF kappa B in FRTL-5 cells. Similarly, hydrolysis of sphingomyelin to ceramide, 
      but not activation of PKC, resulted in an increased in IRF-1 mRNA levels in 
      FRTL-5 cells. The present data demonstrate that IFN gamma and TNF alpha increase 
      IRF-1 mRNA levels in FRTL-5 cells through activation of GAS and NF kappa B 
      binding proteins, respectively. Thus, our results suggest that upregulation of 
      IRF-1 may play a role in mediating the effects of IFN gamma and TNF alpha on 
      thyroid function. Our results also suggest that the induction of IRF-1 mRNA by 
      IFN gamma and TNF alpha is not the cellular mechanism involved in the synergistic 
      effect of these cytokines on thyroid function.
FAU - Mori, K
AU  - Mori K
AD  - Division of Endocrinology, University of Massachusetts Medical Center, Worcester 
      01655, USA.
FAU - Stone, S
AU  - Stone S
FAU - Khaodhiar, L
AU  - Khaodhiar L
FAU - Braverman, L E
AU  - Braverman LE
FAU - DeVito, W J
AU  - DeVito WJ
LA  - eng
GR  - AA11277/AA/NIAAA NIH HHS/United States
GR  - DK18919/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (Irf1 protein, mouse)
RN  - 0 (Irf1 protein, rat)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoproteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - DNA
MH  - DNA-Binding Proteins/*biosynthesis
MH  - Enzyme Activation
MH  - Interferon Regulatory Factor-1
MH  - Interferon-gamma/*pharmacology
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Phosphoproteins/*biosynthesis
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - Protein Kinase C/metabolism
MH  - Rats
MH  - Recombinant Proteins/pharmacology
MH  - Transcription Factors/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1999/07/15 10:00
MHDA- 2000/06/20 09:00
CRDT- 1999/07/15 10:00
PHST- 1999/07/15 10:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/07/15 10:00 [entrez]
AID - 10.1002/(SICI)1097-4644(19990801)74:2<211::AID-JCB7>3.0.CO;2-U [pii]
PST - ppublish
SO  - J Cell Biochem. 1999 Aug 1;74(2):211-9.