Il-1 Beta And Tsh Disturb Thyroid Epithelium Integrity In Autoimmune Thyroid Diseases

Pro-inflammatory cytokines such as IL-1 beta and TNF alpha are known to affect thyroid function. They stimulate IL-6 secretion and modify epithelium integrity by altering junction proteins. To study the role of cytokines on thyroid epithelia tightness in autoimmune thyroid diseases (AITD), we analyzed the expression profiles of junction proteins (ZO-1, Claudin, JAM-A) and cytokines in human thyroid slices and also investigated the effect of IL-1 beta on the epithelium integrity in primary cultures of human thyrocytes. Junction proteins expression (ZO-1, Claudin, JAM-A) has been analyzed by immunohistochemistry on thyroid slices and by Western blot on membrane proteins extracted from thyrocytes of patients suffering from Graves and Hashimoto diseases. The high expression of junction proteins we found on Graves' disease thyroid slices as well as in cell membrane extracts acknowledges the tightness of thyroid follicular cells in this AITD. In contrast, the reduced expression of JAM and ZO-1 in thyroid cells from patients suffering from Hashimoto thyroiditis is in agreement with the loss of thyroid follicular cell integrity that occurs in this pathology. Concerning the effects on epithelium integrity of TSH and of the pro-inflammatory cytokine IL-1 beta in primary cultures of human thyroid cells, TSH appeared able to modify JAM-A localization but without any change in the expression levels of JAM-A, Claudin and ZO-1. Inversely, IL-1 beta provoked a decrease in the expression of-and a redistribution of both, Claudin and ZO-1 without modifying the expression and sub-cellular distribution patterns of JAM-A in thyroid cells. These results demonstrate (i) that Hashimoto's-and Graves' diseases display different junction proteins expression patterns with a loss of epithelium integrity in the former and (ii) that IL-1 beta modifies thyroid epithelial tightness of human thyrocytes by altering the expression and localization of junction proteins. Therefore, IL-1 beta could play a role in the pathogenesis of thyroid autoimmunity. (C) 2012 Elsevier GmbH. All rights reserved.