Search results for "Fas receptor"
showing 5 items of 85 documents
Potential involvement of fas and its ligand in the pathogenesis of Hashimoto's thyroiditis
1997
The mechanisms responsible for thyrocyte destruction in Hashimoto's thyroiditis (HT) are poorly understood. Thyrocytes from HT glands, but not from nonautoimmune thyroids, expressed Fas. Interleukin-1β (IL-1β), abundantly produced in HT glands, induced Fas expression in normal thyrocytes, and cross-linking of Fas resulted in massive thyrocyte apoptosis. The ligand for Fas (FasL) was shown to be constitutively expressed both in normal and HT thyrocytes and was able to kill Fas-sensitive targets. Exposure to IL-1β induced thyrocyte apoptosis, which was prevented by antibodies that block Fas, suggesting that IL-1β-induced Fas expression serves as a limiting factor for thyrocyte destruction. Th…
Retarded thymic involution and massive germinal center formation in NF-ATp-deficient mice.
1998
NF-ATp and NF-ATc are the most prominent nuclear NF-AT transcription factors in peripheral T lymphocytes. After T cell activation both factors bind to and control the promoters and enhancers of numerous lymphokine and receptor ligand genes. In order to define a specific role for NF-ATp in vivo we have inactivated the NF-ATp gene by gene targeting in mice. We show that NF-ATp deficiency leads to the accumulation of peripheral T cells with a “preactivated” phenotype, enhanced immune responses of T cells after secondary stimulation in vitro and severe defects in the proper termination of antigen responses, as shown by a reduced deletion of superantigen-reactive CD4+ T cells. These alterations …
Regulation of Apoptosis in Endocrine Autoimmunity
2002
Dysregulation of apoptosis is associated with the pathogenesis of organ-specific autoimmune diseases, through altered target organ susceptibility. Apoptosis signaling pathways can be initiated through activation of death receptors such as Fas. A comparative analysis of the expression of Fas and FasL, the antiapoptotic molecule Bcl-2, and apoptosis in both thyrocytes and thyroid-infiltrating lymphocytes (TILs) from patients with either Graves' disease (GD) or Hashimoto's thyroiditis (HT) was performed. GD thyrocytes expressed less Fas than HT thyrocytes, whereas GD TILs had higher levels of Fas and FasL than HT TILs. GD thyrocytes expressed higher levels of Bcl-2 compared with HT thyrocytes.…
Possible Pathogenetic Relevance of Interleukin-1beta in "Destructive" Organ-specific Autoimmune Disease (Hashimoto's Thyroiditis)
1999
Thyroid follicular cells (TFC) abundantly express a variety of immunologically relevant surface molecules in Hashimoto's thyroiditis (HT), for example, MHC antigens and adhesion molecules such as ICAM-1. Cytokines produced by infiltrating type 1 helper and cytotoxic T cells are importantly involved in de novo expression or up-regulation of such molecules. We recently demonstrated that TFC from HT patients almost invariably bear on their surface two additive functional molecules: Fas/Apo1/CD95, an important participant in apoptosis, and B7.1, a member of a family of "co-stimulatory" molecules that are crucial for efficient antigen presentation. To date, 12 out of 14 surgical HT thyroid speci…
Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS.
2005
Phosphorylated p38 mitogen-activated protein kinase (p38MAPK), but not activated c-jun-N-terminal kinase (JNK), increases in the motor neurons of transgenic mice overexpressing ALS-linked SOD1 mutants at different stages of the disease. This effect is associated with a selective increase of phosphorylated MKK3-6, MKK4 and ASK1 and a concomitant upregulation of the TNFalpha receptors (TNFR1 and TNFR2), but not IL1beta and Fas receptors. Activation of both p38 MAPK and JNK occurs in the activated microglial cells of SOD1 mutant mice at the advanced stage of the disease; however, this effect is not accompanied by the concomitant activation of the upstream kinases ASK1 and MKK3,4,6, while both …