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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• 作者：Geun-Hee Lee^a ; ¹ ; Mi-Hee Lee^a ; ¹ ; Yeo-Dae Yoon^b ; Jong-Soon Kang^b ; Suhkneung Pyo^c ; Eun-Yi Moon^a ; ^{eunyimoon@sejong.ac.kr} ; ^{eunyimoon@yahoo.com}
• 关键词：BAFF ; B cell activating factor belongs to TNF-伪 family ; ROS ; reactive oxygen species ; FBS ; fetal bovine serum ; NAC ; N-acetyl-L-cysteine ; DCF-DA ; 2&prime ; 7&prime ; -Dichlorodihydrofluorescein diacetate ; PMA ; phorbol 12-myristate 13-acetate ; IOM ; ionomycin
• 刊名：Cytokine
• 出版年：2012
• 期刊代码：97_10434666
• 类别：imm
• 出版时间：July, 2012
• 卷：59
• 期：1
• 页码：115-123
• 文件大小：868 K

摘要

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-魏B 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 1.0 kb hBAFF promoter was higher than that in 0.75, 0.5 or 0.25 kb hBAFF promoter. The existence of three AP-1 binding motifs was computer-analyzed in hBAFF promoter. The stimulation with PMA and ionomycin (IOM) increased 1.0 kb 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 H₂O₂ treatment also enhanced hBAFF promoter activity. c-Fos expression and AP-1 binding to oligonucleotide were reduced by the treatment with NAC. H₂O₂ 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.