Inhibition of caspase cascade by HTLV-I Tax through induction of NF-κB nuclear translocation

NF-kappa B is required for prevention of apoptosis. We examined the importance of human T-cell leukemia virus-1 (HTLV-I) Tax protein to stimulate NF-kappa B nuclear translocation, thus preventing apoptosis. Jurkat cells and JPX-9 cells in which the inducible Tax expression plasmid vector was stably transfected were used in the present study. Both Jurkat and Tax-JPX-9 cells had small amounts of basal nuclear NF-kappa B activity. The addition of NF-kappa B inhibitors suppressed NF-kappa B nuclear translocation of the cells, thus inducing apoptosis. Sequential activation of caspases from caspase-8 to caspase-3 was shown during this process. NF-kappa B nuclear translocation in JPX-9 cells was stimulated through Tax expression, and both the activation of caspases and apoptosis induced by NF-kappa B inhibitors were significantly suppressed in the Tax(+) JPX-9 cells. The expression of Bcl-2, Bar, and Bcl-x was not changed among Jurkat. Tax(-) JPX-9, and Tax(+) JPX-9 cells in the presence or absence of NF-kappa B inhibitors. X-chromosome-linked inhibitor of apoptosis (XIAP) protein expression in Tax(-) JPX-9 cells was significantly suppressed by NF-kappa B inhibitors, however, its expression in Tax(+) JPX-9 cells was maintained even by the addition of NF-kappa B inhibitors. Our results suggest that the activation of NF-kappa B via Tax protein in HTLV-I infected cells renders the cells resistant to apoptosis. The expression of anti-apoptotic gene products such as XIAP to suppress caspase cascade, results in an increase of cytokine production and cell proliferation; one of the proposed mechanisms that promotes autoimmune disorders such as Sjogren's syndrome and rheumatoid arthritis found in HTLV-I seropositive subjects. (C) 1999 by The American Society of Hematology.