CG sequence- and phosphorothioate backbone modification-dependent activation of the NF-kappaB-responsive gene expression by CpG-oligodeoxynucleotides in human RPMI 8226 B cells.
Oligodeoxynucleotides containing CpG motifs (CpG-ODNs) have gained attention because of their stimulatory effects on innate immune responses. CpG-ODN 1826 containing two GACGTT motifs is well known to activate the mouse immune cells while CpG-ODN 2006 containing three GTCGTT motifs is optimal for human cells. We have shown that stimulation of the human B cell line RPMI 8226 with CpG-ODN 1826 or 2006 results in the activation of IL-8 promoter and nuclear localization of NF-kappaB in the CG sequence- and phosphorothioate backbone modification-dependent manner. It was also demonstrated that myeloid differentiation protein and tumor necrosis factor receptor-associated factor 6 are involved in the signal transduction pathway triggered by the CpG-ODNs. Furthermore, phosphorothioate-modified CpG-ODN 1826 led to induce the NF-kappaB-responsive inflammatory cytokine gene expression in the cells. Experimental results indicated that the phosphorothioate derivative of CpG-ODN 1826 not only activates the mouse immune cells, but also stimulates NF-kappaB responsive gene expression in the human B cell line.
Lee
Keun-Wook
KW
Department of Biochemistry, College of Science, Yonsei University, Seoul 120-749, South Korea.
Kim
Doo-Sik
DS
Kwon
Hyung-Joo
HJ
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D013457:Sulfur Compounds / Q000737:chemistry / Q000378:metabolism*; D048029:TNF Receptor-Associated Factor 6
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016209:Interleukin-8; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D011971:Receptors, Immunologic; D013457:Sulfur Compounds; D048029:TNF Receptor-Associated Factor 6