Functional Fas ligand expression in thyrocytes from patients with Graves' disease

Fas/Fas ligand (FasL) interaction has been suggested to play a role in the pathogenesis of Hashimoto's thyroiditis. This manuscript addressed a role f or Fas/FasL interaction in the pathogenesis of Graves' disease (GD). Apopto sis was detected in 0.5-5.0% of GD thyrocytes, but not in normal thyrocytes from patients with adenoma(N). Fas was constitutively expressed on the bas ement membrane of both GD and N thyrocytes. Thyrocytes expressed Bcl-2 cons titutively in both GD and N thyrocytes. Fast was detected at the messenger ribonucleic acid level in thyroid tissue and cultured thyroid cells by Nort hern blotting and RT-PCR. Fast protein was detected in the cytoplasm and ba solateral surface of thyrocytes from GD, but not in N. Cell surface express ion of Fast on cultured thyrocytes disappeared within 48 h after their isol ation. However, it was retained by culturing the cells with a matrix metall oproteinase inhibitor. Coculture with thyrocytes induced apoptosis of Fas t ransfectants, which was blocked by an anti-Fast antibody. Although cultured thyrocytes expressed Fas on the surface, they were not killed by an agonis tic anti-Fas antibody. Interferon-gamma-induced Fas up-regulation was suppr essed by TSH. These results suggest that the increased expression of Fast i n GD thyrocytes, the down-regulation of Fas expression by TSH or possibly b y TSH receptor autoantibody, and the overexpression of Bcl-2, which could r ender thyrocytes resistant to FasL-mediated elimination, may thus be involv ed in the pathogenesis of GD.