Effect of 17 -estradiol on tumor necrosis factor- -induced cytotoxicity in the human peripheral T lymphocytes

We determined the effect of 17 -estradiol on tumor necrosis factor (TNF)-induced cytotoxicity in human peripheral T lymphocytes (T cells) using lactate dehydrogenase assay. Treatment with 17 -estradiol (1–100 nM) for 24 h showed dose-dependent reduction of TNFinduced cytotoxicity in T cells. To further evaluate the mechanism of 17 -estradiol on TNF-induced cytotoxicity in T cells, we identified estrogen receptor (ER) protein in T cells using immunocytochemistry and used the pure ER antagonist ICI 172,780. ER immunoreactivity was clearly observed in T cells. ER immunoreactivity was also detected in some T cells. ICI 172,780 (10 7 M) alone did not affect cytotoxicity in T cells, however, ICI 172,780 (10 7 M) completely abolished 17 -estradiol cytoprotective effects in T cells. TNFtended to increase nuclear factor B (NFB) protein levels in nuclear extracts but it did not reach statistical significance by Western blotting. In contrast, NFB protein levels in nuclear extracts followed by TNFwith 17 -estradiol treatment were significantly increased compared with NFB protein levels in untreated group. NFB blocker pyrrolidinedithiocarbamate (PDTC) (10 4 M) alone did not affect cytotoxicity in T cells. In contrast, PDTC (10 4 M) completely abolished 17 estradiol cytoprotective effects in T cells. Caspase -3/-7 activity was significantly increased followed by TNF, and 17 -estradiol treatment significantly reduced the increment. The present studies suggest the protective effect of 17 -estradiol on TNF-induced cytotoxicity through ERs in T cells and that NFB activation and caspase suppression may be involved in the mechanism. Journal of Endocrinology (2005) 184, 191–197