TAILIEUCHUNG - Báo cáo khóa học: NF-jB- and c-Jun-dependent regulation of human cytomegalovirus immediate-early gene

The cytomegalovirus immediate-early (CMV IE) gene enhancer/promoter regulates the expression of immediate-early gene products and initiation of CMV replication. TNF-aand lipopolysaccharide (LPS) strongly activate the promoter, possibly involving NF-jB. CpG-oligodeoxy-nucleotides (CpG-ODNs), which contain unmethylated CpG dinucleotides in the context of particular base sequences, havegainedattentionbecauseof their stimulating effects, via NF-jB, which have a strong innate immune response. | Eur. J. Biochem. 271 1094-1105 2004 FEBS 2004 doi NF-jB- and c-Jun-dependent regulation of human cytomegalovirus immediate-early gene enhancer promoter in response to lipopolysaccharide and bacterial CpG-oligodeoxynucleotides in macrophage cell line RAW Younghee Lee1 Wern-Joo Sohn3 Doo-Sik Kim2 3 and Hyung-Joo Kwon3 1Cell Biology Laboratory Korea Research Institute of Bioscience and Biotechnology KRIBB Yusong Daejon Korea department of Biochemistry and 3Institute of Life Science and Biotechnology College of Science Yonsei University Seoul Korea The cytomegalovirus immediate-early CMV IE gene enhancer promoter regulates the expression of immediate-early gene products and initiation of CMV replication. TNF-a and lipopolysaccharide LPS strongly activate the promoter possibly involving NF-kB. CpG-oligodeoxy-nucleotides CpG-ODNs which contain unmethylated CpG dinucleotides in the context of particular base sequences have gained attention because of their stimulating effects via NF-kB which have a strong innate immune response. To study the effects of LPS and CpG-ODNs as well as the mechanisms of their actions regarding CMV IE enhancer promoter activation we used a macrophage cell line RAW . Stimulation of the cells with LPS or CpG-ODNs resulted in the activation of the CMV IE enhancer promoter. We examined the involvement of NF-kB and c-Jun transcription factors by promoter deletion site-specific mutation analysis and ectopic expression and found them to have additive effects. Involvement of myeloid differentiation protein an upstream regulator of NF-kB and c-Jun was also investigated. Experimental results indicate that both LPS-induced and CpG-ODN-induced activations of CMV IE enhancer promoter are mediated by Toll-like receptor signaling molecules. Several lines of evidence suggest the potential contribution of bacterial infection in CMV reactivation along with the potential application of CpG-ODNs in gene therapy as a .

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