PMID- 9528954
OWN - NLM
STAT- MEDLINE
DCOM- 19980414
LR  - 20061115
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 139
IP  - 4
DP  - 1998 Apr
TI  - Activation of transcriptionally active nuclear factor-kappaB by tumor necrosis 
      factor-alpha and its inhibition by antioxidants in rat thyroid FRTL-5 cells.
PG  - 1715-22
AB  - ABSTRACT Tumor necrosis factor-alpha (TNF-alpha) exerts pleiotropic effects on 
      thyroid follicular cells. However, the intracellular signaling pathway for the 
      TNF-alpha action has not been well elucidated. The present study examined the 
      effects of TNF-alpha on the activation of nuclear factor-kappa B (NF-kappaB) and 
      on the expression of interleukin (IL)-6 gene in rat thyroid FRTL-5 cells. The 
      treatment of the cells with TNF-alpha resulted in the nuclear translocation of 
      p65-p50 heterodimer as well as p50-p50 homodimer NF-kappaBs. The treatment with 
      the antioxidants 20 mM N-acetyl-L-cysteine (NAC) and 10 microM pyrrolidine 
      dithiocarbamate (PDTC) inhibited the TNF-alpha-dependent activation of p65-p50 
      heterodimer but not the p50-p50 homodimer, indicating that generation of oxidants 
      is required for the activation of the heterodimer NF-kappaB. When the plasmid 
      containing the multimerized NF-kappaB sites upstream of a luciferase reporter 
      gene was transfected into FRTL-5 cells, the treatment with NAC or PDTC prevented 
      the TNF-alpha-dependent increase in the luciferase activities, indicating that 
      the p65-p50 heterodimer is a transcriptionally active NF-kappaB. Accordingly, the 
      TNF-alpha-dependent increase in IL-6 messenger RNA and in secretion of the 
      protein was prevented by the treatment with NAC. These results strongly suggest 
      that TNF-alpha increases the IL-6 gene expression through the activation of 
      NF-kappaB in the thyroid cells, and that antioxidants suppress the 
      TNF-alpha-dependent IL-6 expression by inhibiting the activation of the 
      transcriptionally active NF-kappaB.
FAU - Kikumori, T
AU  - Kikumori T
AD  - Department of Endocrinology and Metabolism, Research Institute of Environmental 
      Medicine, Nagoya University, Japan.
FAU - Kambe, F
AU  - Kambe F
FAU - Nagaya, T
AU  - Nagaya T
FAU - Imai, T
AU  - Imai T
FAU - Funahashi, H
AU  - Funahashi H
FAU - Seo, H
AU  - Seo H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Antioxidants)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Biological Transport
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Dimerization
MH  - Gene Expression
MH  - Humans
MH  - Interleukin-6/genetics
MH  - Luciferases/genetics
MH  - NF-kappa B/antagonists & inhibitors/genetics/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Recombinant Fusion Proteins
MH  - Thyroid Gland/*metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1998/04/07 00:00
MHDA- 1998/04/07 00:01
CRDT- 1998/04/07 00:00
PHST- 1998/04/07 00:00 [pubmed]
PHST- 1998/04/07 00:01 [medline]
PHST- 1998/04/07 00:00 [entrez]
AID - 10.1210/endo.139.4.5874 [doi]
PST - ppublish
SO  - Endocrinology. 1998 Apr;139(4):1715-22. doi: 10.1210/endo.139.4.5874.