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

Objective: Apoptosis via the Fas pathway is a potential mechanism for thyro id tissue destruction leading to clinical hypothyroidism in Hashimoto's thy roiditis (HT). Recent studies reported contradictory results regarding the regulation of Fas/Fas ligand (FasL) expression by cytokines in vitro. We th erefore determined the Fas and East gene expression in the BioBreeding/Worc ester (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 w ithout lymphocytic thyroiditis (LT), rats were divided into 3 groups: 55-da y-old rats after 34 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, Fast, and interleukin (IL)-1 beta was determined Ly Gen escan fragment analysis using reverse polymerase chain reaction. Serum thyr oglobulin (TG) antibody concentrations were measured and the extent of lymp hocytic infiltration of one thyroid lobe was histologically graded. Results: Fas and Fast gene expression was significantly higher in rats with LT and correlated with the extent of lymphocytic infiltration and the TG a ntibody level. There was no evidence that the expression of IL-1 beta or ot her cytokines is related to the expression of Fas or its ligand. Conclusions: The increased expression of Fas and Fast in LT of BB/W rats su ggests 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 B B/W rat Fas/FasL expression is not regulated by IL-2, -4, -6, -10, -12, int erferon gamma, and tumor necrosis factor alpha.