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 for Fas/FasL interaction in the pathogenesis of Graves' disease (GD). Apoptosis was detected in 0.5-5.0% of GD thyrocytes, but not in normal...

Full description

Saved in:
Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 1999-08, Vol.84 (8), p.2896-2902
Main Authors: HIROMATSU, Y, HOSHINO, T, YAGITA, H, KOGA, M, SAKISAKA, S, HONDA, J, DAMU YANG, KAYAGAKI, N, OKUMURA, K, NONAKA, K
Format: Article
Language:English
Subjects:
Adult
Apoptosis
Biological and medical sciences
Cells, Cultured
Endocrinopathies
Fas Ligand Protein
Female
Graves Disease - metabolism
Graves Disease - pathology
Humans
Interferon-gamma - pharmacology
Medical sciences
Membrane Glycoproteins - analysis
Membrane Glycoproteins - genetics
Membrane Glycoproteins - physiology
Middle Aged
Non tumoral diseases. Target tissue resistance. Benign neoplasms
Proto-Oncogene Proteins c-bcl-2 - analysis
RNA, Messenger - analysis
Thyroid Gland - chemistry
Thyroid Gland - cytology
Thyroid. Thyroid axis (diseases)
Thyrotropin - pharmacology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Fas/Fas ligand (FasL) interaction has been suggested to play a role in the pathogenesis of Hashimoto's thyroiditis. This manuscript addressed a role for Fas/FasL interaction in the pathogenesis of Graves' disease (GD). Apoptosis 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 basement membrane of both GD and N thyrocytes. Thyrocytes expressed Bcl-2 constitutively in both GD and N thyrocytes. FasL was detected at the messenger ribonucleic acid level in thyroid tissue and cultured thyroid cells by Northern blotting and RT-PCR. FasL protein was detected in the cytoplasm and basolateral surface of thyrocytes from GD, but not in N. Cell surface expression of FasL on cultured thyrocytes disappeared within 48 h after their isolation. However, it was retained by culturing the cells with a matrix metalloproteinase inhibitor. Coculture with thyrocytes induced apoptosis of Fas transfectants, which was blocked by an anti-FasL antibody. Although cultured thyrocytes expressed Fas on the surface, they were not killed by an agonistic anti-Fas antibody. Interferon-gamma-induced Fas up-regulation was suppressed by TSH. These results suggest that the increased expression of FasL in GD thyrocytes, the down-regulation of Fas expression by TSH or possibly by TSH receptor autoantibody, and the overexpression of Bcl-2, which could render thyrocytes resistant to FasL-mediated elimination, may thus be involved in the pathogenesis of GD.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.84.8.2896