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Transcriptional regulation of major histocompatibility complex class I gene by insulin and IGF-I in FRTL-5 thyroid cells.
Giuliani, C; Saji, M; Bucci, I; Fiore, G; Liberatore, M; Singer, D S; Monaco, F; Kohn, L D; Napolitano, G.
Afiliación
  • Giuliani C; Unit of Endocrinology, Department of Medicine and Sciences of Aging, University G D'Annunzio and Aging Research Center, Ce.S.I., Gabriele D'Annunzio University Foundation, Campus Universitario, via Colle dell'Ara, 66013 Chieti, Italy. cgiulian@unich.it
J Endocrinol ; 189(3): 605-15, 2006 Jun.
Article en En | MEDLINE | ID: mdl-16731791
Increased major histocompatibility complex (MHC) class I gene expression in nonimmune cell 'target tissues' involved in organ-specific diseases may be important in the pathogenesis of autoimmune diseases. This possibility in part evolves from studies of cultured thyrocytes where properties appear relevant to the development of thyroid autoimmune disease. In FRTL-5 rat thyroid cells in continuous culture, hormones and growth factors that regulate cell growth and function specifically decrease MHC class I gene expression. We hypothesized that this could reflect a mechanism to preserve self-tolerance and prevent autoimmune disease. The mechanisms of action of some of these hormones, namely TSH and hydrocortisone, have been already characterized. In this report, we show that IGF-I transcriptionally downregulates MHC class I gene expression and that its action is similar to that of insulin. The two hormones have a complex effect on the promoter of the MHC class I gene, PD1. In fact, they decrease the full promoter activity, but upregulate the activity of deleted mutants that have lost an upstream, tissue-specific regulatory region but still retain the enhancer A region. We show that insulin/IGF-I promotes the interactions of the p50/p65 subunits of NF-kappaB and AP-1 family members with these two regions, and that the tissue-specific region acts as a dominant silencer element on insulin/IGF-I regulation of promoter activity. These observations may be important to understand how MHC class I gene transcription is regulated in the cells.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glándula Tiroides / Transcripción Genética / Factor I del Crecimiento Similar a la Insulina / Genes MHC Clase I / Regulación de la Expresión Génica / Insulina Límite: Animals Idioma: En Revista: J Endocrinol Año: 2006 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glándula Tiroides / Transcripción Genética / Factor I del Crecimiento Similar a la Insulina / Genes MHC Clase I / Regulación de la Expresión Génica / Insulina Límite: Animals Idioma: En Revista: J Endocrinol Año: 2006 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido