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 Hoermann, R. Articles by Schumm-Draeger, P. M. Search for Related Content PubMed PubMed Citation Articles by Hoermann, R. Articles by Schumm-Draeger, P. M.

Regulation of Intercellular Adhesion Molecule-1 Expression in Human Thyroid Cells in Vitro and Human Thyroid Tissue Transplanted to the Nude Mouse in Vivo: Role of Graves’ Immunoglobulins and Human Thyrotropin Receptor¹

Division of Endocrinology, Department of Medicine, University of Essen, D-45122 Essen; the Department of Medicine, University of Munich (C.S., A.E.H.), D-80336 Munich; and the Center of Internal Medicine, University of Frankfurt (P.M.S.), D-60950 Frankfurt am Main, Germany

Address all correspondence and requests for reprints to: Dr. Rudolf Hoermann, Division of Endocrinology, Department of Medicine, University of Essen, Hufelandstrasse 55, D-45122 Essen, Germany.

To further explore a potential role for the human TSH receptor (hTSHR) in the propagation of thyroid autoimmune disease, we examined immunomodulatory effects in response to its stimulation by Graves’ Igs both in human thyroid tissue transplanted to the nude mouse and in primary cultures of human thyrocytes. We injected nude mice bearing transplants derived from normal human thyroid with protein A-Sepharose-purified Graves’ IgGs (0.05–1 mg) on 2 days and assessed, in addition to functional stimulation, the expression of intercellular adhesion molecule-1 (ICAM-1) by transplant thyrocytes. In parallel to functional stimulation, as demonstrated by thyroid follicular cell hypertrophy in the transplants and increased T₄ production, Graves’ IgGs induced a marked dose-dependent expression of ICAM-1 by transplanted thyrocytes, which exceeded that of a continuous interferon- infusion (200 IU/24 h) for 2 days. Normal IgGs were ineffective. Bovine TSH (bTSH) had little effect by itself, but did enhance interferon--induced ICAM-1 expression. To assess the specificity of their effects, experiments with Graves’ IgGs were conducted in the presence and absence of a selective hTSHR antagonist (asialoagalacto-hCG). Asialoagalacto-hCG nearly completely abolished the stimulatory effect of Graves’ IgGs on ICAM-1 expression and significantly reduced the combined bTSH/interferon- effect. It failed, however, to affect interferon- action. In vitro studies using human thyroid cells in primary culture confirmed the in vivo observations; treatment with saline resulted in 14% of cells expressing ICAM-1, with pooled normal IgGs (500 mg/L) in 18% and with Graves’ IgGs (patient A, 448 mg/L; patient B, 260 mg/L) in 78% and 51%, respectively. Upon exposure to Graves’ IgGs (90 mg/L) plus asialo-hCG (350 mg/L), 25% of the cells stained positively for ICAM-1, 29% to bTSH (10 IU/L), 31% to recombinant human TSH (10 IU/L), and 84% to interferon- (10 IU/mL).

In conclusion, stimulation of human thyroid cells, either transplanted to the nude mouse in vivo or studied under in vitro conditions, with Igs derived from patients with Graves’ disease increased the expression of ICAM-1 on the surface of the cells. The action appears to be specific and mediated by the hTSHR. This particular property of TSHR autoantibodies may be of pathophysiological relevance in Graves’ disease, as it may assist in targeting the autoimmune attack and in promoting lymphocyte recruitment to the thyroid gland.

This article has been cited by other articles:

				A. Kretowski, N. Wawrusiewicz, K. Mironczuk, J. Mysliwiec, M. Kretowska, and I. Kinalska Intercellular Adhesion Molecule 1 Gene Polymorphisms in Graves' Disease J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4945 - 4949. [Abstract] [Full Text] [PDF]

				J. Chung, E. S. Park, D. Kim, J. M. Suh, H. K. Chung, J. Kim, H. Kim, S. J. Park, O-Y. Kwon, H. K. Ro, et al. Thyrotropin Modulates Interferon-{gamma}-Mediated Intercellular Adhesion Molecule-1 Gene Expression by Inhibiting Janus Kinase-1 and Signal Transducer and Activator of Transcription-1 Activation in Thyroid Cells Endocrinology, June 1, 2000; 141(6): 2090 - 2097. [Abstract] [Full Text] [PDF]

				S. Costagliola, N. G. Morgenthaler, R. Hoermann, K. Badenhoop, J. Struck, D. Freitag, S. Poertl, W. Weglöhner, J. M. Hollidt, B. Quadbeck, et al. Second Generation Assay for Thyrotropin Receptor Antibodies Has Superior Diagnostic Sensitivity for Graves' Disease J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 90 - 97. [Abstract] [Full Text]

				P. J. Simons, F. G. A. Delemarre, and H. A. Drexhage Antigen-Presenting Dendritic Cells as Regulators of the Growth of Thyrocytes: A Role of Interleukin-1{beta} and Interleukin-6 Endocrinology, July 1, 1998; 139(7): 3148 - 3156. [Abstract] [Full Text] [PDF]