Relationship between constitutive nuclear factor-kappaB (NF-κB) and inhibitor kappaB-alpha (IκB-α) in an interferon-α-sensitive human Burkitt lymphoma cell line

The human Burkitt lymphoma Daudi cell line expresses constitutively active nuclear factor kappaB (NF-κB) in the nucleus in spite of high levels of inhibitor kappaB-alpha (IκB-α) in the cytoplasm. The antiproliferative response of these cells to interferon-α (IFN-α) correlated with the inhibition of the constitutive NF-κB activity by the cytokine. The present study shows that IFN-α caused an increase in p53 level, inhibited cell proliferation by [3H]thymidine incorporation, and stimulated cytotoxicity and apoptosis by PARP-cleavage in the Daudi cells. In order to study the relationship between the constitutively active NF-κB and IκB-α, a dominant negative mutant IκB-α (IκB-αDN), lacking the N-terminal 36 amino acids required for the activation of NF-κB by tumor necrosis factor-α (TNF-α), was expressed in the Daudi cells. The expression of IκB-αDN protein did not inhibit the constitutive NF-κB activity, but it inhibited cell proliferation, antiproliferative response to IFN-α, and phosphorylated mitogen activated protein kinase (p-MAPK) level. Thus, our results suggest that constitutive NF-κB activity in the human Burkitt lymphoma Daudi cells is maintained by a mechanism independent of IκB-α degradation, and that the IκB-α is involved in the proliferation of these cells, possibly through the MAP kinase pathway. Therefore, in addition to IFN-α treatment, both NF-κB and IκB-α may be used as drug targets for inhibiting cell proliferation in the lymphomas.