Hormonal Regulation of the MHC Class I Gene in Thyroid Cells: Role of the Promoter “Tissue-Specific” Region

Abstract

In previous studies we have demonstrated that the expression of the Major Histocompatibility Complex (MHC) class I gene in thyrocytes is controlled by several hormones, growth factors, and drugs. These substances mainly act on two regions of the MHC class I promoter a “tissue-specific” region (−800 to −676 bp) and a “hormone/cytokines-sensitive” region (−500 to −68 bp). In a previous study, we have shown that the role of the “tissue-specific” region in the MHC class I gene expression is dominant compared to that of the “hormone/cytokines-sensitive” region. In the present report we further investigate the dominant role of the “tissue-specific” region evaluating the effect of thyroid stimulating hormone (TSH), methimazole (MMI), phenylmethimazole (C10), glucose and thymosin-α1. By performing experiments of electrophoretic mobility shift assays (EMSAs) we show that TSH, MMI and C10, which inhibit MHC class I expression, act on the “tissue-specific” region increasing the formation of a silencer complex. Glucose and thymosin-α1, which stimulate MHC class I expression, act decreasing the formation of this complex. We further show that the silencer complex is formed by two distinct members of the transcription factors families activator protein-1 (AP-1) and nuclear factor-kB (NF-kB), c-jun and p65, respectively. These observations are important in order to understand the regulation of MHC class I gene expression in thyroid cells and its involvement in the development of thyroid autoimmunity.

The Tumor Microenvironment and the Estrogen Loop in Thyroid Cancer

“…In this respect, Giuliani et al demonstrated that MHC reduction was associated with high levels of TGF-β1, and αand γ-interferons (IFNs). Other negative MHC regulators included insulin and insulin-like growth factor receptor (IGF)-1, Thyroid Stimulating Hormone (TSH), methimazole, phenyl methimazole, thymosin-α1 and glucose [29].…”