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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 3 945-952
Copyright © 1998 by The Endocrine Society


Original Studies

Cytokines and Thyroid Epithelial Integrity: Interleukin-1{alpha} Induces Dissociation of the Junctional Complex and Paracellular Leakage in Filter-Cultured Human Thyrocytes1

Mikael Nilsson2, Johanna Husmark, Ulla Björkman and Lars E. Ericson

Institute of Anatomy and Cell Biology, Göteborg University, S-413 90 Göteborg, Sweden

Address all correspondence and requests for reprints to: Mikael Nilsson, Institute of Anatomy and Cell Biology, Göteborg University, Box 420, (SE) 405 30, Göteborg, Sweden. E-mail: mikael.olof.nilsson{at}anat.cell.gu.se

Locally produced proinflammatory cytokines are likely to play a pathophysiological role in autoimmune thyroid disease. An important feature of the thyroid, not previously considered in cytokine actions, is the barrier created by the follicular epithelium, which secludes two lumenal autoantigens [thyroglobulin (Tg) and thyroperoxidase] from the extrafollicular space. We examined the influence of recombinant cytokines on the barrier function of human thyrocytes cultured as a tight and polarized monolayer in bicameral chambers. Whereas interleukin (IL)-6 (100 U/mL), interferon-{gamma} (100 U/mL), tumor necrosis factor-{alpha} (10 ng/mL), and transforming growth factor-ß1 (10 ng/mL) had no effects, exposure to IL-1{alpha} for 24–48 h reduced the transepithelial resistance from >1000 to <50 {Omega} x cm2 and increased the paracellular flux of [3H]inulin and exogeneous 125I-Tg. This response to IL-1{alpha}, which was dose dependent (1–1000 U/mL) and reversible, was accompanied by dramatic morphological changes of the epithelial junction complex, including aberrant localization of the tight junction protein zonula occludens-1. At the same time, IL-1{alpha} decreased the apical secretion of endogeneous Tg and stimulated the basolateral release of a novel high-molecular-mass protein. We conclude that IL-1{alpha} reduces the thyroid epithelial barrier without signs of general cytotoxicity. The observation suggests a mechanism by which IL-1{alpha} may promote the exposure of hidden autoantigens to the immune system in thyroid autoimmunity.




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