TY - JOUR
T1 - Antiproliferative effects of IFN-α correlate with the downregulation of nuclear factor-κB in human Burkitt lymphoma Daudi cells
AU - Rath, P. C.
AU - Aggarwal, B. B.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1089/10799900152434402
DO - 10.1089/10799900152434402
M3 - Article
C2 - 11506747
AN - SCOPUS:0034827441
SN - 1079-9907
VL - 21
SP - 523
EP - 528
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
IS - 7
ER -