Fas/Fas ligand up-regulation and Bcl-2 down-regulation may be significant in the pathogenesis of Hashimoto's thyroiditis.
Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by diffuse thyroid lymphocytic infiltration and follicle destruction. Cross-linking of the Fas receptor with its own ligand (FasL) triggers apoptosis in various systems, whereas the Bcl-2 protooncogene inhibits apoptotic cell death. The involvement of Fas, FasL, and Bcl-2 in the apoptotic process in HT was evaluated in 15 thyroid tissue samples from patients with HT stained for apoptosis and for Fas, FasL, and Bcl-2 protein expression. Eight samples from healthy thyroid tissue were used for comparison. Thyroid follicles in HT samples exhibited strong staining for Fas and FasL and a high percentage of apoptosis (30.3 +/- 14.5%, mean +/- SD), in contrast to normal control follicles that exhibited moderate Fas, minimal or no FasL, and hardly any apoptosis. Immunostaining for Bcl-2 was high in normal, and weak in involved, thyroid follicles. Infiltrating lymphocytes stained weakly for FasL and strongly for Bcl-2. We conclude that follicular cells in HT undergo apoptosis by concomitant up-regulation of FasL and Fas and down-regulation of Bcl-2 protein. The lymphocytes do not seem to be directly engaged in the process with their own FasL, but they may provide the appropriate cytokine milieu that, in turn, up-regulates Fas and/or FasL leading to apoptosis.
Mitsiades
N
N
Laboratory of Pathology, National Institutes of Health, Bethesda, Maryland 20892, USA. nmitsiad@box-n.nih.gov
Poulaki
V
V
Kotoula
V
V
Mastorakos
G
G
Tseleni-Balafouta
S
S
Koutras
D A
DA
Tsokos
M
M
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D003432:Cross-Linking Reagents; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism*
D003432:Cross-Linking Reagents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor