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

It has been shown that interferon-gamma (IFN gamma) 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 IFN gamma (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 IFN gamma. IFN gamma alone had not effect on either basal TG secretion or de novo TG synthesis, as measured by immunoprecipitation. At 100 U/mL and above, IFN gamma inhibited TSH-induced TG secretion into the medium. At 500 U/mL, IFN gamma inhibited TSH- or dibutyryl cAMP-induced TG synthesis at the gene transcription level, as evidenced by the decrease in steady state TG mRNA. IFN gamma 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 IFN gamma directly inhibits TSH-stimulated TG gene expression and TG secretion. This provides further evidence that IFN gamma has a metabolic effect on thyroid hormone synthesis.