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.