Type I Interferons modulate the expression of thyroid peroxidase, sodium/iodide symporter, and thyroglobulin genes in primary human thyrocyte cultures

We evaluated in primary human thyrocyte cultures the effect of interferon (IFN)-alpha and -beta on the expression of thyroid peroxidase (TPO), sodium/iodide symporter (NIS), and thyroglobulin (Tg) as well as T-4 release. Human thyrocyte cultures were carried out with fresh normal thyroid tissue. Gene and protein expression of Tg, TPO, and NIS were assessed by RT-PCR and Western blot analysis after 24, 48, and 72 h of treatment with TSH alone (10 mIU/ml) and in combination with IFNalpha or -beta (10(4) U/ml). IFN inhibited the TSH-stimulated gene expression of Tg, TPO, and NIS in a time-dependent manner without significant differences between IFNalpha and -beta. Moreover, the addition of both type I IFNs clearly reduced the TSH-stimulated protein expression of Tg, TPO, and NIS after 72 h of exposure. Finally, this down-regulation was associated with a reduction of T-4 release by almost 50%. In conclusion, our study shows that both IFNalpha and -beta down-regulate the TSH-stimulated expression of Tg, TPO, and NIS as well as T-4 release. Indeed, the development of hypothyroidism during type I IFN therapy may be related, at least in part, to an abnormal expression and function of key proteins involved in iodine uptake and organification.