RGD Reference Report - Fas/FasL mediated apoptosis of thyrocytes in Graves' disease. - Rat Genome Database

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Fas/FasL mediated apoptosis of thyrocytes in Graves' disease.

Authors: Sera, N  Kawakami, A  Nakashima, T  Nakamura, H  Imaizumi, M  Koji, T  Abe, Y  Usa, T  Tominaga, T  Ejima, E  Ashizawa, K  Yokoyama, N  Ishikawa, N  Ito, K  Eguchi, K 
Citation: Sera N, etal., Clin Exp Immunol. 2001 May;124(2):197-207.
RGD ID: 8662820
Pubmed: PMID:11422195   (View Abstract at PubMed)
PMCID: PMC1906041   (View Article at PubMed Central)

We examined in the present study the possible involvement of Fas and its ligand (FasL) in the process of Graves' disease. Immunohistochemical analysis showed that few normal thyrocytes expressed Fas but many thyrocytes in Graves' disease expressed this molecule. The percentage of FasL-positive thyrocytes in Graves' thyroids was, however, less than in normal thyroids. Several apoptotic thyrocytes and infiltrating mononuclear cells (MNCs) were detected scattered throughout Graves' thyroid tissues and abundant proliferating cell nuclear antigen (PCNA)-positive thyrocytes were present. Apoptotic cells, as well as PCNA-positive cells, were scarcely detectable in normal thyroid glands, however. In vitro treatment of thyrocytes by IL-1beta a cytokine found to be expressed in Graves' thyroid glands, increased Fas but reduced FasL expression. IL-1beta-stimulated thyrocytes became sensitive to apoptosis by anti-Fas IgM monoclonal antibody (mAb). Activated T cells, which strongly expressed FasL, showed cytotoxic activity toward IL-1beta-stimulated thyrocytes but not toward unstimulated thyrocytes. This cytotoxic activity involved the Fas/FasL pathway. Importantly, unstimulated thyrocytes could kill activated, but not resting, T cells. IL-1beta-stimulated thyrocytes, with down-regulated FasL expression, could not efficiently kill activated T cells. The cytotoxic activity of unstimulated thyrocytes toward activated T cells was inhibited by anti-FasL mAb. Interestingly, unstimulated thyrocytes induced apoptosis in IL-1beta-stimulated thyrocytes but not in unstimulated thyrocytes. These interactions were also blocked by anti-FasL mAb. Our results suggest that the apoptotic cell death of both thyrocytes and infiltrating MNCs found in Graves' thyroid glands is regulated by IL-1beta through Fas/FasL interactions.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Graves' disease  IEP 8662820protein:increased expression:thyroid gland and thyrocyte (human)RGD 
Graves' disease  ISOFAS (Homo sapiens)8662820; 8662820protein:increased expression:thyroid gland and thyrocyte (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fas  (Fas cell surface death receptor)

Genes (Mus musculus)
Fas  (Fas cell surface death receptor)

Genes (Homo sapiens)
FAS  (Fas cell surface death receptor)


Additional Information