Antiproliferative Effects of IFN- α Correlate with the Downregulation of Nuclear Factor- κ B in Human Burkitt Lymphoma Daudi Cells

Abstract

Interferon-α (IFN-α) is known to exhibit antiviral, antiproliferative, and immunomodulatory properties through mechanisms still not fully understood. Nuclear transcription factor-κB(NF-κB) plays a major role in viral replication, cell proliferation, and immune response. Whether antiproliferative effects of IFN are mediated through suppression of NF-κB is not known. We, therefore, examined the relationship between the antiproliferative effects of IFN-α and NF-κB activity in a human Burkitt lymphoma Daudi cell line. These cells were found to constitutively express high levels of active NF-κB that cannot be further activated by tumor necrosis factor (TNF). Treatment of cells with IFN-α suppressed the activated NF-κB in a dose-dependent manner, with an optimum effect at 10 U/ml in 72 h. Suppression of NF-κB correlated with a concomitant decrease in the cytoplasmic levels of IκBα, the inhibitory protein of NF-κB, known to be regulated by NF-κB. Downregulation of constitutive NF-κB activity correlated with a decrease in cell proliferation by IFN-α. Overall, our results suggest that IFN-α is a potent suppressor of constitutive NF-κB, which may contribute to the inhibition of cell proliferation.