1,25-Dihydroxyvitamin D{sub 3} induces biphasic NF-{kappa}B responses during HL-60 leukemia cells differentiation through protein induction and PI3K/Akt-dependent phosphorylation/degradation of I{kappa}B

Journal Article · Tue May 01 00:00:00 EDT 2007 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2007.02.022· OSTI ID:20972151

Tse, A K.-W. ^[1]; Wan, C -K ^[2]; Shen, X -L ^[2]; Zhu, G -Y ^[1]; Cheung, H -Y ^[2]; Yang, M ^[2]; Fong, W -F ^[1]

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1. Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong (China)
2. Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Hong Kong (China)

1,25-Dihydroxyvitamin D{sub 3} (VD{sub 3}) induces differentiation in a number of leukemia cell lines and under various conditions is able to either stimulate or inhibit nuclear factor kappa B (NF-{kappa}B) activity. Here we report a time-dependent biphasic regulation of NF-{kappa}B in VD{sub 3}-treated HL-60 leukemia cells. After VD{sub 3} treatment there was an early {approx} 4 h suppression and a late 8-72 h prolonged reactivation of NF-{kappa}B. The reactivation of NF-{kappa}B was concomitant with increased IKK activities, IKK-mediated I{kappa}B{alpha} phosphorylation, p65 phosphorylation at residues S276 and S536, p65 nuclear translocation and p65 recruitment to the NF-{kappa}B/vitamin D responsive element promoters. In parallel with NF-{kappa}B stimulation, there was an up-regulation of NF-{kappa}B controlled inflammatory and anti-apoptotic genes such as TNF{alpha}, IL-1{beta} and Bcl-xL. VD{sub 3}-triggered reactivation of NF-{kappa}B was associated with PI3K/Akt phosphorylation. PI3K/Akt antagonists suppressed VD{sub 3}-stimulated I{kappa}B{alpha} phosphorylation as well as NF-{kappa}B-controlled gene expression. The early {approx} 4 h VD{sub 3}-mediated NF-{kappa}B suppression coincided with a prolonged increase of I{kappa}B{alpha} protein which require de novo protein synthesis, lasted for as least 72 h and was insensitive to MAPK, IKK or PI3K/Akt inhibitors. Our data suggest a novel biphasic regulation of NF-{kappa}B in VD{sub 3}-treated leukemia cells and our results may have provided the first molecular explanation for the contradictory observations reported on VD{sub 3}-mediated immune-regulation.

• OSTI ID: 20972151
• Journal Information: Experimental Cell Research, Vol. 313, Issue 8; Other Information: DOI: 10.1016/j.yexcr.2007.02.022; PII: S0014-4827(07)00096-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOSYNTHESIS
CELL DIFFERENTIATION
CYCLOHEXIMIDE
GENES
INFLAMMATION
LEUKEMIA
PHOSPHORYLATION
PHOSPHOTRANSFERASES
RECEPTORS
TIME DEPENDENCE
VITAMIN D