Fas and Fas ligand gene expression in autoimmune thyroiditis in BB/W rats.
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)-1beta 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-1beta 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 gamma, and tumor necrosis factor alpha.
Blüher
M
M
III Medical Department, Faculty of Medicine, University of Leipzig, Germany.
Krohn
K
K
Wallaschofski
H
H
Braverman
L E
LE
Paschke
R
R
D000818:Animals; D001706:Biopsy; D004247:DNA / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification; D051381:Rats; D011913:Rats, Inbred BB; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018709:Statistics, Nonparametric; D013954:Thyroglobulin / Q000097:blood; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
D017931:DNA Primers; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019014:fas Receptor; D012313:RNA; D004247:DNA; D013954:Thyroglobulin