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1,25-Dihydroxyvitamin D 3 induces biphasic NF-κB responses during HL-60 leukemia cells differentiation through protein induction and PI3K/Akt-dependent phosphorylation/degradation of IκB

Tse, Anfernee Kai-Wing ; Wan, Chi-Keung ; Shen, Xiao-Ling ; Zhu, Guo-Yuan ; Cheung, Hon-Yeung ; Yang, Mengsu ; Fong, Wang-Fun

Experimental cell research, 2007-05, Vol.313 (8), p.1722-1734 [Periódico revisado por pares]

Elsevier Inc

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  • Título:
    1,25-Dihydroxyvitamin D 3 induces biphasic NF-κB responses during HL-60 leukemia cells differentiation through protein induction and PI3K/Akt-dependent phosphorylation/degradation of IκB
  • Autor: Tse, Anfernee Kai-Wing ; Wan, Chi-Keung ; Shen, Xiao-Ling ; Zhu, Guo-Yuan ; Cheung, Hon-Yeung ; Yang, Mengsu ; Fong, Wang-Fun
  • Assuntos: 1,25-Dihydroxyvitamin D 3 ; IKK ; Leukemia ; Monocytic differentiation ; NF-κB
  • É parte de: Experimental cell research, 2007-05, Vol.313 (8), p.1722-1734
  • Descrição: 1,25-Dihydroxyvitamin D 3 (VD 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-κB) activity. Here we report a time-dependent biphasic regulation of NF-κB in VD 3-treated HL-60 leukemia cells. After VD 3 treatment there was an early ∼ 4 h suppression and a late 8–72 h prolonged reactivation of NF-κB. The reactivation of NF-κB was concomitant with increased IKK activities, IKK-mediated IκBα phosphorylation, p65 phosphorylation at residues S276 and S536, p65 nuclear translocation and p65 recruitment to the NF-κB/vitamin D responsive element promoters. In parallel with NF-κB stimulation, there was an up-regulation of NF-κB controlled inflammatory and anti-apoptotic genes such as TNFα, IL-1β and Bcl-xL. VD 3-triggered reactivation of NF-κB was associated with PI3K/Akt phosphorylation. PI3K/Akt antagonists suppressed VD 3-stimulated IκBα phosphorylation as well as NF-κB-controlled gene expression. The early ∼ 4 h VD 3-mediated NF-κB suppression coincided with a prolonged increase of IκBα 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-κB in VD 3-treated leukemia cells and our results may have provided the first molecular explanation for the contradictory observations reported on VD 3-mediated immune-regulation.
  • Editor: Elsevier Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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