PMID- 22090273
OWN - NLM
STAT- MEDLINE
DCOM- 20120409
LR  - 20120207
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 97
IP  - 2
DP  - 2012 Feb
TI  - Overexpression of metallothionein I/II: a new feature of thyroid follicular cells 
      in Graves' disease.
PG  - 446-54
LID - 10.1210/jc.2011-1429 [doi]
AB  - CONTEXT: 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. METHODOLOGY: 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-gamma 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-gamma-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.
FAU - Ruiz-Riol, M
AU  - Ruiz-Riol M
AD  - Laboratory of Immunobiology for Research and Applications to Diagnosis, 
      Universitat Autonoma de Barcelona, 08916 Badalona, Spain.
FAU - Martinez-Arconada, M J
AU  - Martinez-Arconada MJ
FAU - Alonso, N
AU  - Alonso N
FAU - Soldevila, B
AU  - Soldevila B
FAU - Marchena, D
AU  - Marchena D
FAU - Armengol, M P
AU  - Armengol MP
FAU - Sanmarti, A
AU  - Sanmarti A
FAU - Pujol-Borrell, R
AU  - Pujol-Borrell R
FAU - Martinez-Caceres, E M
AU  - Martinez-Caceres EM
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20111116
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 9038-94-2 (Metallothionein)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Cells, Cultured
MH  - Cohort Studies
MH  - Female
MH  - Gene Expression Regulation
MH  - Graves Disease/*genetics/metabolism/pathology
MH  - Humans
MH  - Male
MH  - Metallothionein/*genetics/metabolism
MH  - Middle Aged
MH  - Stress, Physiological/genetics/physiology
MH  - Thyroid Gland/*metabolism/pathology
MH  - Up-Regulation/genetics
MH  - Young Adult
EDAT- 2011/11/18 06:00
MHDA- 2012/04/10 06:00
CRDT- 2011/11/18 06:00
PHST- 2011/11/18 06:00 [entrez]
PHST- 2011/11/18 06:00 [pubmed]
PHST- 2012/04/10 06:00 [medline]
AID - jc.2011-1429 [pii]
AID - 10.1210/jc.2011-1429 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2012 Feb;97(2):446-54. doi: 10.1210/jc.2011-1429. Epub 
      2011 Nov 16.