Pc. Rath et Bb. Aggarwal, Antiproliferative effects of IFN-alpha correlate with the downregulation of nuclear factor-kappa B in human Burkitt lymphoma Daudi cells, J INTERF CY, 21(7), 2001, pp. 523-528
Interferon-alpha (IFN-alpha) is known to exhibit antiviral, antiproliferati
ve, and immunomodulatory properties through mechanisms still not fully unde
rstood. Nuclear transcription factor-kappa B (NF-kappaB) plays a major role
in viral replication, cell proliferation, and immune response. Whether ant
iproliferative effects of IFN are mediated through suppression of NF-kappaB
is not known. We, therefore, examined the relationship between the antipro
liferative effects of IFN-alpha and NF-kappaB activity in a human Burkitt l
ymphoma Daudi cell line. These cells were found to constitutively express h
igh levels of active NF-kappaB that cannot be further activated by tumor ne
crosis factor (TNF). Treatment of cells with IFN-alpha suppressed the activ
ated NF-kappaB in a dose-dependent manner, with an optimum effect at 10 U/m
l in 72 h. Suppression of NF-kappaB correlated with a concomitant decrease
in the cytoplasmic levels of I kappaB alpha, the inhibitory protein of NF-k
appaB, known to be regulated by NF-kappaB. Downregulation of constitutive N
F-kappaB activity correlated with a decrease in cell proliferation by IFN-a
lpha. Overall, our results suggest that IFN-alpha is a potent suppressor of
constitutive NF-kappaB, which may contribute to the inhibition of cell pro
liferation.