Interleukin-1 beta modulates thyrotropin-induced thyroglobulin mRNA transcription through 3',5'-cyclic adenosine monophosphate.
It has been reported that interleukin-1 possesses not only immunoregulatory action, but also multiple hormone like effects. We studied the action of recombinant interleukin-1 beta (IL-1 beta) on the synthesis of thyroglobulin (TG), the precursor of thyroid hormone. Human thyrocytes dispersed from normal and Graves' thyroid tissues were incubated with TSH with or without IL-1 beta. TSH stimulated TG release from cultured human thyrocytes after 4 days. This effect was mimicked by dibutyryl cAMP (dBcAMP). IL-1 beta had no effect on basal TG release but modulates the TSH-stimulated TG secretion. At low dose (10(-5) to 10(-3) U/ml) IL-1 beta increased the TSH-stimulated TG secretion while higher doses (1-100 U/ml) of IL-1 beta had an inhibitory effect. Similar responses were observed with both normal and Graves' thyrocytes. The effect of IL-1 beta occurred at the gene transcription level as reflected by changes in TG mRNA level. At 100 U/ml, IL-1 beta suppressed TG mRNA level to near unmeasurable level. This biphasic effect of IL-1 beta on TG synthesis is paralleled by a similar change in TSH-stimulated cAMP secretion. We conclude that IL-1 beta possesses hormonal action on TG gene transcription and its effect is mediated via cAMP.
Kung
A W
AW
Department of Medicine, University of Hong Kong, Queen Mary Hospital.
Lau
K S
KS
D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects; D006111:Graves Disease / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D013954:Thyroglobulin / Q000235:genetics* / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003994:Bucladesine; D013972:Thyrotropin; D013954:Thyroglobulin; D000242:Cyclic AMP