Abstract
Apoptosis, i.e. natural programmed cell death, is a physiological phenomenon indispensable for normal functioning of the organism. The signal to apoptosis can be started practically in any cell. Disturbances in the apoptosis regulation determine the essential link of the pathogenesis of many diseases, including autoimmune thyroid disorders.
The aim of the study was to assess the expression of Fas/FasL and caspase eight in the tissues of the thyroid gland in patients with Graves' disease (GD), non-toxic nodular goiter (NTNG) and Hashimoto's thyroiditis (HT). The analysis of Fas/FasL expression was performed by western blot and immunohistochemical investigation with DAB-visualization and Mayer's hematoxylin staining. Caspase-8 expression in thyroid follicular cells was assayed by western blot method.
Identification of the proapoptotic proteins FasL and Fas exhibited their pronounced expression in the thyroid tissue in GD patients (++; ++) and HT (+++; +++) as compared to the NTNG group (0/+; 0/+). Among the study groups, the expression of caspase-8 was revealed in band 55 kDa from patients with autoimmune thyroid diseases.
In GD patients, the percentage of thyrocytes with FasL expression correlated positively with TRAb (R = 0.58, p < 0.02). However, no such correlations were noted in HT or non-toxic multinodular goiter. There were no significant correlations between thyroid hormones and the percentage of thyrocytes with Fas and FasL expression.
In conclusion, our findings suggest that the changes in the expression of apoptotic molecules on the surface of T lymphocytes and thyroid follicular cells in patients with autoimmune thyroid disorders reflect their substantial involvement in the pathogenesis of GD and HT. In addition, analysis of Fas/FasL and caspase-8 expression in thyroid tissue may indicate the disease activity and immunological phenotype.
Abbreviations | ||
PerCP | = | peridinin chlorophyll protein |
FITC | = | fluorescein isothiocyanate |
PE | = | phycoerythrin |
fT3 | = | free triiodothyronine |
fT4 | = | free thyroxine |
TSH | = | thyroid stimulating hormone |
TRAbs | = | antibodies against receptor for thyroid stimulating hormone |
TPO-Abs | = | antithyroid peroxidase antibodies |
hTPO | = | human thyroid peroxidase |
TG-Abs | = | antithyroglobulin antibodies |
AITD | = | autoimmune thyroid disease |
GD | = | Graves' disease |
NTMG | = | non-toxic multinodular goiter |
HT | = | Hashimoto's thyroiditis |
mAb | = | monoclonal antibodies |
TFC | = | thyroid follicular cell |
ITLs | = | intrathyroidal T lymphocytes |
Abbreviations | ||
PerCP | = | peridinin chlorophyll protein |
FITC | = | fluorescein isothiocyanate |
PE | = | phycoerythrin |
fT3 | = | free triiodothyronine |
fT4 | = | free thyroxine |
TSH | = | thyroid stimulating hormone |
TRAbs | = | antibodies against receptor for thyroid stimulating hormone |
TPO-Abs | = | antithyroid peroxidase antibodies |
hTPO | = | human thyroid peroxidase |
TG-Abs | = | antithyroglobulin antibodies |
AITD | = | autoimmune thyroid disease |
GD | = | Graves' disease |
NTMG | = | non-toxic multinodular goiter |
HT | = | Hashimoto's thyroiditis |
mAb | = | monoclonal antibodies |
TFC | = | thyroid follicular cell |
ITLs | = | intrathyroidal T lymphocytes |
Acknowledgements
We thank Mrs Anna Łyczkowska (Department of Biochemistry and Molecular Biology, Medical Center of Postgraduate Education, Warsaw, Poland) and Mrs Jolanta Czerwinska (Department of Pathomorphology, Medical Center of Postgraduate Education, Warsaw, Poland), for valuable suggestions and contribution to this study.
Notes
The work was presented at XVI Symposium of Polish Society of Pediatric Endocrinology (PSPE) in Białowieża, 28–30.09.2006 and at the Conference of European Society of Pediatric Endocrinology (ESPE), 30.06.2006–03.07.2006, Rotterdam, Holland.