Protein kinase C stimulates human B cell activating factor gene expression through reactive oxygen species-dependent c-Fos in THP-1 pro-monocytic cells

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Title
Protein kinase C stimulates human B cell activating factor gene expression through reactive oxygen species-dependent c-Fos in THP-1 pro-monocytic cells
Author(s)
G H Lee; M H Lee; Yeo Dae YoonJong Soon Kang; S Pyo; E Y Moon
Bibliographic Citation
Cytokine, vol. 59, no. 1, pp. 115-123
Publication Year
2012
Abstract
BAFF is associated with various immunological diseases. Previously, we have reported that mouse B cell activating factor (mBAFF) expression was dependent on nuclear localization of co-activator, p300 and the activation of transcription factors including NF-κB and CREB. Here, we investigated whether transcription factor, c-Fos, regulates human (h) BAFF expression through promoter activation by PMA-induced reactive oxygen species (ROS) production. We cloned hBAFF promoter into luciferase-expressing pGL3-basic vector. The activity of 1.0kb hBAFF promoter was higher than that in 0.75, 0.5 or 0.25kb hBAFF promoter. The existence of three AP-1 binding motifs was computer-analyzed in hBAFF promoter. The stimulation with PMA and ionomycin (IOM) increased 1.0kb hBAFF promoter activity, time-dependently. PMA/IOM-stimulation rapidly enhanced c-Fos expression in THP-1 human pro-monocytic cells. Binding of c-Fos to hBAFF promoter was detected by chromatin immunoprecipitation (ChIP) assay. hBAFF expression and its promoter activity were decreased by the transfection with small interference (si) RNA of c-Fos. ROS production in THP-1 cells was increased by PMA/IOM-stimulation. In addition, hBAFF activity stimulated by PMA/IOM was reduced by N-acetyl-cysteine (NAC), a well-known ROS scavenger. Serum starvation (0.5% FBS) producing ROS and the exogenous H 2O 2 treatment also enhanced hBAFF promoter activity. c-Fos expression and AP-1 binding to oligonucleotide were reduced by the treatment with NAC. H 2O 2 was not able to induce hBAFF expression in the presence of staurosporine, PKC inhibitor. Data suggest that hBAFF expression could be regulated by promoter activation through c-Fos association, which might be dependent on PMA-induced ROS production.
Keyword
C-FosHBAFFPKCPromoterROS
ISSN
1043-4666
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.cyto.2012.03.017
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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