Fas and Fas ligand gene expression in autoimmune thyroiditis in BB/W rats

Abstract

Objective: Apoptosis via the Fas pathway is a potential mechanism for thyroid tissue destruction leading to clinical hypothyroidism in Hashimoto's thyroiditis (HT). Recent studies reported contradictory results regarding the regulation of Fas/Fas ligand (FasL) expression by cytokines in vitro. We therefore determined the Fas and FasL gene expression in the BioBreeding/Worcester (BB/W) rat thyroiditis model, which can be regarded as a model for HT. Methods: In order to obtain BB/W rats with spontaneous, iodine-induced or without lymphocytic thyroiditis (LT), rats were divided into 3 groups: 55-day-old rats after 24 days of iodine administration, 75-day-old rats after 45 days of iodine administration, and 101-day-old rats respectively. The gene expression of Fas, FasL, and interleukin (IL)-1b was determined by Genescan fragment analysis using reverse polymerase chain reaction. Serum thyroglobulin (TG) antibody concentrations were measured and the extent of lymphocytic infiltration of one thyroid lobe was histologically graded. Results: Fas and FasL gene expression was significantly higher in rats with LT and correlated with the extent of lymphocytic infiltration and the TG antibody level. There was no evidence that the expression of IL-1b or other cytokines is related to the expression of Fas or its ligand. Conclusions:The increased expression of Fas and FasL in LT of BB/W rats suggests the involvement of the Fas pathway in the pathogenesis of LT in BB/W rats. However, in contrast to results of recent in vitro studies, in the BB/W rat Fas/FasL expression is not regulated by IL-2, -4, -6, -10, -12, interferon g, and tumor necrosis factor a.

Effect of iodide on Fas, Fas-ligand and Bcl-w mRNA expression in thyroid of NOD mice pretreated with methimazole

“…Accordingly, the iodine-induced elevated expression of this apoptosis-related gene could play an important role also in the model of experimental thyroiditis in NOD mice. Our results agree with those of Bluher et al (22), who described high expression of Fas-L in BB/W rats after iodide administration. However, these authors have also detected an increase in Fas expression in comparison with control animals.…”

“…The mechanisms involved have been related to direct toxicity as a consequence of high peroxide levels due to the strong expression of thyroid peroxidase in goiter-inducing conditions (7,21). Recently, many authors have related iodine to the development of apoptosis in humans (10,11) or in experimental models (22).…”

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“…The infiltration of activated scavenger macrophages into the thyroid follicles, thus destroying the thyroid cells, is compatible with T H1 -mediated mechanisms [59]. Fas and Fas ligand (FasL) expression was higher in rats with lympholytic thyroiditis indicating a role of these apoptotic molecules in thyrocyte death [60]. …”

The role of apoptosis in autoimmune thyroid disorders and thyroid cancer

“…Production of interleukin 1β during thyroid inflammation induced upregulation of Fas expression and apoptosis in thyrocytes 20. In in vivo studies of BioBreeding/Worcester rats, Fas and FasL gene expression significantly increased in lymphocytic thyroiditis 21. Further animal studies showed that administration of plasmid DNA coding for FasL in thyroid follicular cells inhibited development of lymphocytic infiltration of the thyroid and induced the death of infiltrating T cells 22.…”