Interferon-γ inhibits thyrotropin-induced thyroglobulin gene transcription in cultured human thyrocytes

Abstract

It has been shown that interferon-γ (IFNγ) can induce HLA class II antigen expression by thyroid epithelial cells and may play a role in the pathogenesis of autoimmune thyroid disease. We have examined the metabolic effect of recombinant human IFNγ (0.001-500 U/mL) on thyroglobulin (TG) synthesis and secretion in cultured human thyrocytes. Thyrocytes dispersed from human Graves' thyroid tissues were cultured in the presence of TSH with or without IFNγ. IFNγ alone had not effect on either basal TG secretion or de novo TG synthesis, as measured by immunoprecipitation. At 100 U/mL and above, IFNγ inhibited TSH-induced TG secretion into the medium. At 500 U/mL, IFNγ inhibited TSH- or dibutyryl cAMP-induced TG synthesis at the gene transcription level, as evidenced by the decrease in steady state TG mRNA. IFNγ had no effect on either basal or TSH-induced cAMP release by the thyrocytes, suggesting that the inhibitory effect occurs at a site distal to cAMP formation. These data demonstrate that IFNγ directly inhibits TSH-stimulated TG gene expression and TG secretion. This provides further evidence that IFNγ has a metabolic effect on thyroid hormone synthesis.