Role of Death Receptor Pathway in Estradiol-Induced T-Cell Apoptosis in Vivo

• DOI: 10.1093/toxsci/70.1.63
• Publication Date: 2002-10-18T22:05:25Z
• Authors: Y. Do
• Keywords: Fas ligand

In the current study we investigated mechanism by which β-estradiol-17-valerate (E2) induces apoptosis in T cells. To this end, C57BL/6 wild-type (+/+), Fas-deficient (C57BL/6-lpr/lpr), and FasL-deficient (C57BL/6-gld/gld) mice were treated with various concentrations of E2, including 75, 25, 5, 1, or 0.1 mg/kg body weight vehicle. The thymi from these harvested on days 4, 7 following treatment, cellularity determined. Treatment E2 caused a decrease thymic at all doses except three groups mice, particularly 4 7. Interestingly, however, degree atrophy C57BL/6-lpr/lpr C57BL/6-gld/gld was significantly less than that seen mice. When thymocytes analyzed for apoptosis, cells showed decreased levels apoptosis. Moreover, cDNA array analysis gene expression revealed treatment upregulated several genes involved FasL, caspases, TRAIL, iNOS, but not bcl-2 family. Reverse transcriptase-polymerase chain reaction data also demonstrated increased Fas FasL treatment. Caspase 8 inhibitor blocked E2-induced vitro. These suggested may induce activating death-receptor rather mitochondrial pathway. expansion peripheral Vβ3+ to bacterial superantigen SEA vivo their subsequent vitro proliferative response SEA, thereby suggesting induction suggests trigger death receptor pathway cells, inducing