Interleukin-1 inhibits thyrotrophin-induced human thyroglobulin gene expression.
The regulation of thyroglobulin (Tg) and its specific mRNA by interleukin-1 (IL-1) in cultured human thyrocytes was investigated. Specific binding of 125I-labelled IL-1 on thyrocytes was confirmed by solid-phase binding assay. Thyrocytes dispersed from Graves' thyroid tissues were incubated with TSH with or without recombinant human IL-1. TSH stimulated Tg release from cultured human thyrocytes in a dose- and time-dependent manner. Both IL-1 alpha and beta inhibited TSH-induced Tg release at concentrations ranging from 0.01 to 10 U/ml. The suppressive activities of IL-1 alpha and beta were similar. They did not alter the basal level of Tg release. Unstimulated human thyrocytes did not contain any detectable Tg mRNA, but TSH-stimulated thyrocytes expressed a single species of Tg mRNA (8.5 kb). Both IL-1 alpha and beta inhibited TSH-induced Tg mRNA in a dose-responsive manner. IL-1 (10 U/ml) caused maximal suppression of TSH-induced Tg mRNA to nearly basal levels. In contrast, the gamma-actin mRNA hybridization signal was not altered in control or treated cells. Furthermore, IL-1 stimulated [3H]thymidine uptake into thyrocyte DNA. These results demonstrate that IL-1 directly inhibits TSH-induced Tg gene expression and provide further support for a functional role of IL-1 as a local modulator of thyroid hormone synthesis.
Yamashita
S
S
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Kimura
H
H
Ashizawa
K
K
Nagayama
Y
Y
Hirayu
H
H
Izumi
M
M
Nagataki
S
S
D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000037:antagonists & inhibitors*
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013972:Thyrotropin; D004247:DNA; D013954:Thyroglobulin