Cadmium Induces Fas Down-Regulation in a Human Immature T-cell Line

Cadmium (Cd²⁺) is an ubiquitous toxic metal with apoptotic and genotoxic effects, which has been involved in a variety of pathological conditions inducing disturbance of the immune system. In the present study we treated the Fas-expressed human immature T-cell line CCRF-CEM with 10μM Cd²⁺ for 6h or 24h. We found that pretreatment of the cells with Cd²⁺ for 24h inhibited apoptosis induced by Fas-ligation with the CH-11 antibody, in contrast to pretreatment for 6h. Immunocytochemical and multiplex RT-PCR analyses indicated that Cd²⁺ treatment for 24h inhibited Fas expression at the transcriptional level. To investigate that effect of Cd²⁺, cDNA microarray analysis was applied, which indicated that the rapid induction of NF-kB, ERK5 and JAK3 genes by Cd²⁺ was the initial step resulting in Fas down-regulation. The Fas down-regulation induced by Cd²⁺ seems to be responsible for the carcinogenic and the immunomodulatory effects of that metal.