title: Overexpression of metallothionein I/II: a new feature of thyroid follicular cells in Graves' disease.
abstract: BACKGROUND
  One salient feature of autoimmune thyroid disease is the inappropriate expression of human leukocyte antigen (HLA) class II molecules by thyroid follicular cells. Metallothioneins (MT) are small proteins induced by tissue stress that can contribute to restoring homeostasis of tissue inflammation and have been found to be increased in a transcriptomic analysis of Graves' disease (GD) glands.
  
  
  METHODS
  To assess the role of MT in the pathogenesis of GD, we analyzed MT-I and -II expression and distribution in GD-affected thyroid glands (n = 14) compared with other thyroid diseases (n = 20) and normal thyroid glands (n = 5). Two-color indirect immunofluorescence and semiquantitative morphometry were applied. The relationship between MT and HLA class II expression was analyzed by their degree of colocalization in GD sections, and in vitro induction kinetics and expression of these molecules on the HT93 thyroid cell line were compared by quantitative RT-PCR and flow cytometry using interferon-γ and zinc as stimuli.
  
  
  RESULTS
  MT were clearly overexpressed in nine of 14 GD glands. MT expression distribution in GD was almost reciprocal to that of HLA class II. In vitro analysis of MT and HLA class II demonstrated that MT is induced more slowly and at a lower level than HLA. Moreover, the main MT inducer, zinc, reduces interferon-γ-induced class II expression.
  
  
  CONCLUSIONS
  These findings show that MT and HLA class II play very different roles in the autoimmune process by affecting the thyroid gland, thereby pointing to the possible role of MT as a marker of cell stress and homeostasis restoration in GD.
authors.affiliation: Laboratory of Immunobiology for Research and Applications to Diagnosis, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ruiz-Riol
authors.forename: M J
authors.initials: MJ
authors.lastname: Martínez-Arconada
authors.forename: N
authors.initials: N
authors.lastname: Alonso
authors.forename: B
authors.initials: B
authors.lastname: Soldevila
authors.forename: D
authors.initials: D
authors.lastname: Marchena
authors.forename: M P
authors.initials: MP
authors.lastname: Armengol
authors.forename: A
authors.initials: A
authors.lastname: Sanmartí
authors.forename: R
authors.initials: R
authors.lastname: Pujol-Borrell
authors.forename: E M
authors.initials: EM
authors.lastname: Martínez-Cáceres
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D006111:Graves Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: D008668:Metallothionein