Regulation of major histocompatibility complex gene expression in thyroid epithelial cells by methimazole and phenylmethimazole
| Autor: | Giorgio Napolitano, Valeria Montani, Ines Bucci, Cesidio Giuliani, Dinah S. Singer, F. Monaco, Leonard D. Kohn |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Response element Genes MHC Class II Thyroid Gland Gene Expression Genes MHC Class I chemical and pharmacologic phenomena Major histocompatibility complex Response Elements Article Cell Line Interferon-gamma Endocrinology Antithyroid Agents Interferon Internal medicine Gene expression MHC class I medicine Cyclic AMP Animals Gene Silencing Receptor Promoter Regions Genetic Gene Thyroid Epithelial Cells Methimazole biology Thiones Epithelial Cells DNA Rats Inbred F344 Recombinant Proteins Rats biology.protein Transcription Initiation Site medicine.drug |
| Zdroj: | The Journal of endocrinology. 204(1) |
| ISSN: | 1479-6805 |
| Popis: | Increased expression of major histocompatibility complex (MHC) class-I genes and aberrant expression of MHC class-II genes in thyroid epithelial cells (TECs) are associated with autoimmune thyroid diseases. Previous studies have shown that methimazole (MMI) reduces MHC class-I expression and inhibits interferon-γ (IFN-γ or IFNG as listed in the MGI Database)-induced expression of the MHC class-II genes in TECs. The action of MMI on the MHC class-I genes is transcriptional, but its mechanism has not been investigated previously. In the present study, we show that in Fisher rat thyroid cell line 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 cAMP response element (CRE)-like site. Furthermore, we show that C10 decreases MHC class-I gene expression to a greater extent than MMI and at 10- to 50-fold lower concentrations. C10 also reduces the IFN-γ-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. |
| Databáze: | OpenAIRE |
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