Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 359, Issue 1-2, Pages 183-191Publisher
SPRINGER
DOI: 10.1007/s11010-011-1013-0
Keywords
ZNF580; H2O2; NF-kappa B; Inflammation; IL-8
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Funding
- Chinese National Natural Science Foundation [30770885]
- Tianjin Natural Science Foundation [10JCYBJC26500]
- Science Foundation of CPAF Medical College [WYZ2007-2]
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ZNF580, a newly found C2H2 zinc finger transcription factor, was first described by Zhang (GenBank ID: AF184939). Emerging evidence has suggested that reactive oxygen species (ROS) play an important role in redox-sensitive signal transduction, and the vascular endothelium plays a critical role in the vascular inflammatory response. In this communication, we present evidence for the potential role of ZNF580 in hydrogen peroxide (H2O2)-regulated inflammation-related signaling pathways. In a human endothelial cell hybridoma line (EA.hy926), ZNF580 levels were markedly upregulated with H2O2 stimulation in different concentrations (0-400 mu M) and at different time-points (0-6 h). H2O2 promoted the rapid translocation of p65 from the cytoplasm into the nucleus according to immunocytochemistry staining. In subsequent research, inhibition of NF-kappa B by pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF-kappa B) was shown to block the upregulated expression of ZNF580 that was induced by H2O2. Furthermore, transient transfection of ZNF580 resulted in an increase of the pro-inflammatory cytokine interleukin-8 (IL-8) 3.01 +/- A 0.05 folds according to real-time RT-PCR and ELISA assays, which also showed significantly enhanced motility of human acute monocytic leukemia cells (THP-1). These results suggest that H2O2 upregulates the expression of ZNF580 via the NF-kappa B signaling pathway, and overexpression of ZNF580 plays a critical role in augmenting the release of pro-inflammatory cytokine IL-8.
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