Up-regulated expression of genes encoding Hrk and IL-3R beta subunit by TCDD in vivo and in vitro.

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been known for its immunosuppressive activity, the mechanisms of its action have been difficult to elucidate, partly because of its inability of exerting its effects in vitro. To gain insights into the molecular mechanisms of immunosuppressive effects of TCDD, we screened for genes, which are regulated by in vivo TCDD treatment in an allogeneic mouse tumor model. RNA, collected from lymphoid organs, was reverse-transcribed to cDNA and hybridized to DNA arrays. In addition to genes such as NF-kappa B p65 and p27(Kip1) which were previously shown to be regulated by TCDD, expression of several genes including Hrk and IL-3R beta (AIC-2A) was shown to be modulated. RT-PCR and Western blot analyses confirmed the differential expression of Hrk and IL-3R beta. Finally, Hrk was up-regulated by TCDD in Jurkat T cells, suggesting the potential role of Hrk in thymic atrophy and the possibility of exploiting Jurkat T cells as a suitable in vitro model for studying mechanisms of thymic atrophy.