Major histocompatibility complex class I gene expression in rat thyroid cells is regulated by hormones, methimazole, and iodide as well as interferon.

Abstract

Autoimmune thyroid disease is associated with enhanced expression of major histocompatibility complex class I antigens on thyrocytes. To better understand this phenomenon, we have studied the normal expression of class I genes in FRTL-5 rat thyroid cells. A variety of hormones and growth factors that regulate the growth and function of these thyroid cells were found to decrease class I RNA levels: serum, insulin or insulin-like growth factor-I (IGF-I), and hydrocortisone. Antibody preparations from Graves' patients (thyroid-stimulating antibodies), which increase cAMP levels and stimulate the thyroid, also decrease class I RNA levels. This is consistent with the fact that TSH, via its cAMP signal, reduces class I transcripts. The class I response to TSH, serum, insulin, IGF-I, or hydrocortisone is specific, in that the same agents do not similarly affect TSH receptor, thyroglobulin, thyroid peroxidase, malic enzyme, or beta-actin RNA levels. Both gamma- and alpha-interferon increase class I RNA levels in FRTL-5 cells, even in the presence of the serum, IGF-I, or hormones noted above, i.e. they overcome hormonal negative regulation in normal thyrocytes. In contrast, methimazole treatment of rat FRTL-5 thyroid cells, but not rat fibroblasts or rat FRT thyroid cells, which have no TSH receptor and no TSH-regulated function, results in reduced class I RNA levels. The action of methimazole can inhibit interferon action, is transcriptional, is duplicated by iodide, and is additive with the negative regulatory action of hormones and serum factors, including TSH.

Enhancement of immunogenicity of tumor cells by cotransfection with genes encoding antisense insulin-like growth factor-1 and B7.1 molecules

“…Down-regulation of MHC class I expression on rat thyroid tumor cells has been reported to occur through the action of IGF-1. 32 Neutralizing IGF-1 with Ab fails to restore MHC class I expression or make the cells immunogenic. In addition to enhancing the expression of MHC class I molecules on cell surfaces, transfection with IGF-1 antisense cDNA may directly enhance Ag processing and presentation by tumor cells and may lead to the production of cytokines or chemokines that are essential for T-cell activation.…”

Phenyl Methimazole Inhibits TNF-α-Induced VCAM-1 Expression in an IFN Regulatory Factor-1-Dependent Manner and Reduces Monocytic Cell Adhesion to Endothelial Cells

“…Northern blot analysis was performed in a manner similar to that described previously (27,29,33). HAEC were washed with PBS, and total RNA was extracted using a commercial kit (RNeasy Mini Kit; Qiagen, Valencia, CA).…”

Thyroglobulin: A Master Regulator of Follicular Function via Transcriptional Suppression of Thyroid Specific Genes.

“…Maximal stimulation by TSH increases TG expression about twofold [19,26]. Physiological concentrations of TG suppresses TG RNA to 1/10th their original levels [26,31].…”

“…Various hormones and cytokines regulate thyroid specific or ubiquitous genes in FRTL-5 cells [12,[18][19][20]30], however, no one had previously recognized a strong regulatory activity by an intrinsic thyroid factor other than TSH. The ability of TG to decrease TSHR and TTF-1 RNA levels were additive to the suppressive action of TSH on these two genes [26].…”