Interleukin-1β modulates thyrotropin-induced thyroglobulin mRNA transcription through 3',5'-cyclic adenosine monophosphate

Abstract

It has been reported that interleukin-1 possesses not only immunoregulatory action, but also multiple hormone like effects. We studied the action of recombinant interleukin1β (IL-1β) on the synthesis of thyroglobulin (TG), the precursor of thyroid hormone. Human thyrocytes dispersed from normal and Graves' thyroid tissue were incubated with TSH with or without IL-1β. TSH stimulated TG release from cultured human thyrocytes after 4 days. This effect was mimicked by dibutyryl cAMP (dBcAMP). IL-1β 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-1β increased the TSH-stimulated TG secretion while higher doses (1-100 U/ml) of IL-1β had an inhibitory effect. Similar responses were observed with both normal and Graves' thyrocytes. The effect of IL-1β occurred at the gene transcription level as reflected by changes in TG mRNA level. At 100 U/ml, IL-1β suppressed TG mRNA level to near unmeasurable level. This biphasic effect of IL-1β on TG synthesis is paralleled by a similar change in TSH-stimulated cAMP secretion. We conclude that IL-1β possesses hormonal action on TG gene transcription and its effect is mediated via cAMP.