title: Effect of type I interferon(s) on cell viability and apoptosis in primary human thyrocyte cultures.
abstract: BACKGROUND
  Interferon (IFN) therapy may induce a generalized activation of the immune system, hence triggering or exacerbating autoimmune disease. Apoptosis contributes to the development of hypothyroidism in autoimmune thyroiditis. IFN can affect all phases of the cell cycle and may induce apoptosis in several cell lines from varied histologies. To date, no data exist on the possible effect of type I IFN(s) on FAS/FASL system and cell apoptosis of human thyroid follicles. Therefore, we evaluated the effect of both IFN-alpha and -beta on apoptosis in primary human thyrocyte cultures and the potential role of the FAS/FASL pathway.
  
  
  METHODS
  Thyrocytes were cultured in monolayers and FAS, FASL, and Bcl-2 mRNA expression was determined by reverse transcriptase polymerase chain reaction after exposure to 10 mIU/mL bovine thyroid-stimulating hormone alone or in combination with increasing doses of IFN-alpha or -beta for 24, 48, and 72 hours. The percentage of apoptotic hypodiploid cells was evaluated by flow cytometry.
  
  
  RESULTS
  Thyroid-stimulating hormone significantly decreased FAS and increased Bcl-2 mRNA expression while reducing the percentage of hypodiploid cells. The concomitant addition of either IFN-alpha or -beta reduced cell viability and increased the number of hypodiloid cells, but only IFN-beta modulated the expression of FAS and Bcl-2 mRNA expression in a proapoptotic sense.
  
  
  CONCLUSIONS
  Both type I IFN(s) increase apoptosis in primary thyrocyte cultures, but only IFN-beta modulates FAS and Bcl-2 gene expression toward a proapoptotic pathway. Because apoptosis plays an important role in thyroid homeostasis and disease, this mechanism may contribute to the development and progression of type I IFN(s) therapy-associated thyroid disease.
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Pisa, Pisa, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Caraccio
authors.forename: Sabina
authors.initials: S
authors.lastname: Cuccato
authors.forename: Federico
authors.initials: F
authors.lastname: Pratesi
authors.forename: Angela
authors.initials: A
authors.lastname: Dardano
authors.forename: Silvia
authors.initials: S
authors.lastname: Ursino
authors.forename: Daniele
authors.initials: D
authors.lastname: Chimenti
authors.forename: Laura
authors.initials: L
authors.lastname: Boldrini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Materazzi
authors.forename: Paola
authors.initials: P
authors.lastname: Migliorini
authors.forename: Fabio
authors.initials: F
authors.lastname: Monzani
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation; D053222:Fas Ligand Protein / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D013959:Thyroid Diseases / Q000139:chemically induced; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects; D013972:Thyrotropin / Q000494:pharmacology; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D053222:Fas Ligand Protein; D007370:Interferon Type I; D016898:Interferon-alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019014:fas Receptor; D016899:Interferon-beta; D013972:Thyrotropin