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 IFN alpha 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 IFN alpha 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 IFN alpha 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.
Caraccio
N
N
Metabolism and Endocrinology Unit, Department of Internal Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy. n.caraccio@int.med.unipi.it
Giannini
R
R
Cuccato
S
S
Faviana
P
P
Berti
P
P
Galleri
D
D
Dardano
A
A
Basolo
F
F
Ferrannini
E
E
Monzani
F
F
D002478:Cells, Cultured; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics*; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013972:Thyrotropin / Q000494:pharmacology; D013974:Thyroxine / Q000502:physiology; D000099209:Sodium-Iodide Symporters
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007453:Iodide Peroxidase; D012333:RNA, Messenger; D011994:Recombinant Proteins; D027981:Symporters; D013954:Thyroglobulin; D013972:Thyrotropin; D013974:Thyroxine; D000099209:Sodium-Iodide Symporters