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This Article Full Text Full Text (PDF) All Versions of this Article: 291/2/E242    most recent 00439.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Gérard, A.-C. Articles by Colin, I. M. Search for Related Content PubMed PubMed Citation Articles by Gérard, A.-C. Articles by Colin, I. M.

Expression of TPO and ThOXs in human thyrocytes is downregulated by IL-1/IFN-, an effect partially mediated by nitric oxide

¹Unité de Morphologie Expérimentale, Université catholique de Louvain; and ²Unité de Biologie Cellulaire, International Institute of Cellular and Molecular Pathology, Université catholique de Louvain, Brussels, Belgium

Submitted 12 September 2005 ; accepted in final form 9 February 2006

Morphological and functional alterations in Hashimoto's thyroiditis (HT) are predominantly mediated by Th1 cytokines through apoptotic cell death. This ultimate step could be preceded by functional injuries in thyroid hormone synthesis. The action of two Th1 cytokines (IL-1/IFN-) on thyroperoxidase (TPO) and thyroid oxidase (ThOXs) expression was tested in human thyrocytes isolated from normal tissues, Graves' disease (GD) tissues, and autonomous toxic nodules. There was no evidence of cell death. Nitric oxide (NO) release was induced by cytokines but was absent when N^G-nitro-L-arginine methyl ester (L-NAME) was coincubated. When thyrotropin (TSH)-incubated normal and GD thyrocytes were treated with IL-1/IFN-, TPO and ThOXs protein and mRNA expression dropped, a decrease partially prevented by L-NAME, suggesting that NO acts as a mediator of Th1 effects. In thyrocytes from autonomous toxic nodules, the high level of TPO and ThOXs protein expression was not influenced by TSH or by cytokines, a finding partially reproduced when normal thyrocytes were treated with increasing concentrations of TSH. In conclusion, incubation of normal or GD thyrocytes with Th1 cytokines induces a significant reduction in TSH-increased expression of both TPO and ThOXs, an effect partially mediated by NO. The thyroid cell function can therefore be severely affected in HT, even when cells remain viable. In autonomous toxic nodules, cells become partially insensitive to exogenous Th1 cytokines.

Th1 cytokines; Hashimoto's thyroiditis; thyroid oxidase; thyroperoxidase; interleukin-1; interferon-