This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hiromatsu, Y. Articles by Nonaka, K. Search for Related Content PubMed PubMed Citation Articles by Hiromatsu, Y. Articles by Nonaka, K.

Functional Fas Ligand Expression in Thyrocytes from Patients with Graves’ Disease

Division of Endocrinology and Metabolism, Department of Medicine (Y.H., M.K., D.Y., K.N.), Department of Immunology (T.H.), and Department of Internal Medicine (S.S., J.H.), Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011; and the Department of Immunology, Juntendo University School of Medicine (H.Y., N.K., K.O.), 2–1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Address all correspondence and requests for reprints to: Yuji Hiromatsu, M.D., Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan. E-mail: yuji{at}med.kurume-u.ac.jp

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--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.

This article has been cited by other articles:

				J.-Y. Hsiao, M.-C. Hsieh, C.-T. Hsiao, H.-H. Weng, and D.-S. Ke Association of CD40 and thyroglobulin genes with later-onset Graves' disease in Taiwanese patients Eur. J. Endocrinol., November 1, 2008; 159(5): 617 - 621. [Abstract] [Full Text] [PDF]

				S. Fountoulakis, G. Vartholomatos, N. Kolaitis, S. Frillingos, G. Philippou, and A. Tsatsoulis Differential expression of Fas system apoptotic molecules in peripheral lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis. Eur. J. Endocrinol., June 1, 2008; 158(6): 853 - 859. [Abstract] [Full Text] [PDF]

				Y. Kitasato, T. Hoshino, M. Okamoto, S. Kato, Y. Koda, N. Nagata, M. Kinoshita, H. Koga, D.-Y. Yoon, H. Asao, et al. Enhanced Expression of Interleukin-18 and its Receptor in Idiopathic Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., December 1, 2004; 31(6): 619 - 625. [Abstract] [Full Text] [PDF]

				H. Tang, K. Chen, Y. Wei, G. C. Sharp, L. McKee, and H. Braley-Mullen Apoptosis of thyrocytes and effector cells during induction and resolution of granulomatous experimental autoimmune thyroiditis Int. Immunol., December 1, 2000; 12(12): 1629 - 1639. [Abstract] [Full Text] [PDF]

				J. R. Baker Jr. Editorial: Dying (Apoptosing?) for a Consensus on the Fas Death Pathway in the Thyroid J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2593 - 2595. [Full Text]