Although the potent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been well known for its immunosuppressive activity, the mechanisms of its action have been difficult to eluci-date. This is partly due to its inability to exert its ef-fects in vitro. To further elucidate the underlying mechanisms of TCDD effects, we screened for genes that are regulated by the in vivo TCDD treatment of mice that are challenged with allogeneic tumor cells. RNA, collected from lymphoid organs including the thymus, draining lymph nodes, and bone marrow, was reverse-transcribed to cDNA and hybridized to DNA arrays that consisted of 588 genes (ClonTech, USA). The expression of the NF-kB p65, c-jun, and p27Kip1 genes was increased by the TCDD treatment, as previ-ously reported. In addition, we found that the expres-sion of several genes, which were not reported as regu-lated by TCDD, were modulated by TCDD. Some genes, including insulin-like growth factor-binding protein-6 (IGFBP-6) and IL-5R alpha, were up-regulated; while other genes, including CD14, were down-regulated. The expression of the IGFBP-6 and IL-5R a subunit genes by TCDD in the thymus was confirmed by RT-PCR and Western blot analyses. Furthermore, TCDD effects on the expression of the IGFBP-6 gene was also observed with EL4 mouse thymoma cells. This suggests that IGFBP-6 may be involved in thymic atrophy, and EL4 cells may be used as an in vitro model for studying molecular mecha-nisms of thymic atrophy.

Keywords: TCDD, IL-5R alpha, Up-Regu-lation., IGFBP-6