Antiproliferative effects of IFN-alpha correlate with the downregulation of nuclear factor-kappa B in human Burkitt lymphoma Daudi cells.
Interferon-alpha (IFN-alpha) is known to exhibit antiviral, antiproliferative, and immunomodulatory properties through mechanisms still not fully understood. Nuclear transcription factor-kappaB (NF-kappaB) plays a major role in viral replication, cell proliferation, and immune response. Whether antiproliferative effects of IFN are mediated through suppression of NF-kappaB is not known. We, therefore, examined the relationship between the antiproliferative effects of IFN-alpha and NF-kappaB activity in a human Burkitt lymphoma Daudi cell line. These cells were found to constitutively express high levels of active NF-kappaB that cannot be further activated by tumor necrosis factor (TNF). Treatment of cells with IFN-alpha suppressed the activated NF-kappaB in a dose-dependent manner, with an optimum effect at 10 U/ml in 72 h. Suppression of NF-kappaB correlated with a concomitant decrease in the cytoplasmic levels of IkappaBalpha, the inhibitory protein of NF-kappaB, known to be regulated by NF-kappaB. Downregulation of constitutive NF-kappaB activity correlated with a decrease in cell proliferation by IFN-alpha. Overall, our results suggest that IFN-alpha is a potent suppressor of constitutive NF-kappaB, which may contribute to the inhibition of cell proliferation.
Rath
P C
PC
Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Aggarwal
B B
BB
D002051:Burkitt Lymphoma / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D020672:I-kappa B Proteins; D016898:Interferon-alpha; D016328:NF-kappa B