Interferon-gamma inhibits thyrotropin-induced thyroidal peroxidase gene expression in cultured human thyrocytes.
We have previously demonstrated that interferon-gamma (IFN-gamma) induced HLA-DR antigen and also inhibited thyrotropin (TSH)-induced triiodothyronine (T3) and thyroglobulin (Tg) secretion from cultured human thyrocytes. In order to further clarify the inhibitory effect of IFN-gamma on TSH-stimulated thyroid hormone secretion, we have examined human thyroid peroxidase (TPO) gene expression. Thyrocytes dispersed from Graves' thyroid tissues were incubated with TSH with or without IFN-gamma. Total RNA was extracted, separated and hybridized with 32P-labelled human TPO cDNA. Thyrocytes expressed four TPO mRNA transcripts (4.0, 3.2, 2.1 and 1.7kb, respectively), all of which were stimulated by TSH. IFN-gamma inhibited TSH-stimulated TPO mRNA in a dose dependent manner (0.01-10U/mL). 1 U/mL IFN-gamma caused maximal suppression of TSH-stimulated TPO mRNA levels to basal levels. IFN-gamma also inhibited 8-bromo-cyclic AMP-stimulated TPO mRNA levels. In contrast, the gamma-actin mRNA hybridization signal was not altered in control or treated cells. These results demonstrate that IFN-gamma directly inhibits TSH-stimulated TPO gene expression and provide further support for a role of IFN-gamma as a local modulator of thyroid hormone synthesis.
Ashizawa
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Yamashita
S
S
Nagayama
Y
Y
Kimura
H
H
Hirayu
H
H
Izumi
M
M
Nagataki
S
S
D002478:Cells, Cultured; D015342:DNA Probes; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D009195:Peroxidase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013961:Thyroid Gland / Q000201:enzymology*; D013972:Thyrotropin / Q000037:antagonists & inhibitors*
D015342:DNA Probes; D012333:RNA, Messenger; D007371:Interferon-gamma; D013972:Thyrotropin; D009195:Peroxidase