| Title | Regulation of major histocompatibility complex gene expression in thyroid epithelial cells by methimazole and phenylmethimazole. | | Author(s) | Giuliani C, Bucci I, Montani V, Singer D, Monaco F, Kohn L, Napolitano G | | Institution | C Giuliani, University "G. DAnnunzio" Chieti, Unit of Endocrinology, Chieti, Italy. | | Source | J Endocrinol 2009 Oct 16. | | Abstract | Increased expression of major histocompatibility complex (MHC) class-I genes and aberrant expression of MHC class-II genes in thyroid epithelial cells (TECs) is associated with autoimmune thyroid diseases. Previous studies have shown that methimazole (MMI) reduces MHC class-I expression and inhibits interferon-gamma (IFN-gamma)-induced expression of the MHC class-II gene in TECs. The action of MMI on the MHC class-I gene is transcriptional, but its mechanism has not been previously investigated. In the present study, we show that in Fisher rat thyroid cell line 5 (FRTL-5) cells, the ability of MMI and its novel derivative phenylmethimazole (C10) to decrease MHC class-I promoter activity is similar to TSH/cAMP suppression of MHC class-I and TSH receptor genes, and involves a 39-bp silencer containing a CRE-like site. Furthermore, we show that C10 decreases MHC class-I gene expression to a greater extent than MMI and at 10-fold to 50-fold lower concentrations. C10 also reduces the IFN-gamma-induced increase in the expression of MHC class-I and MHC class-II genes more effectively than MMI. Finally, we show that in comparison to MMI, C10 is a better inhibitor of specific protein-DNA complexes that are formed with a CRE-like element on the MHC class-II promoter. These data support the conclusion that the immunosuppressive mechanism by which MMI and C10 inhibit MHC gene expression mimics "normal" hormonal suppression by TSH/cAMP. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19837722 |
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