Enhancement of immunomodulatory activity by liposome-encapsulated natural phosphodiester bond CpG-DNA in a human B cell line.
Natural phosphodiester bond CpG-DNA that contains immunomodulatory CpG motifs (PO-DNA) upregulates the expression of proinflammatory cytokines and induces an Ag-driven Th1 response in a CG sequence-dependent manner in mice. In humans, only phosphorothioate backbone-modified CpG-DNA (PS-DNA) and not PO-DNA has immunomodulatory activity. In this study, we found that liposome-encapsulated PO-DNA upregulated the expression of human Beta-defensin-2 (hBD-2) and major histocompatibility class II molecules (HLA-DRA) in a CG sequence-dependent and liposome- dependent manner in human B cells. Of the three different liposomes, DOTAP has the unique ability to enhance the immunomodulatory activity of PO-DNA. In contrast, HLA-DRA and hBD-2 promoter activation can be induced by liposomeencapsulated PS-DNA in a CG sequence-independent manner, depending on the CpG-DNA species. Our observations demonstrate that, when encapsulated with a proper liposome in the immune system, natural PO-DNA has the potential to be a useful therapy for the regulation of the innate immune response.
Kim
Dongbum
D
Department of Microbiology, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
Rhee
Jae Won
JW
Kwon
Sanghoon
S
Kim
Young-Eun
YE
Choi
Soo-Young
SY
Park
Jinseu
J
Lee
Younghee
Y
Kwon
Hyung-Joo
HJ
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D018899:CpG Islands; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D008081:Liposomes; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D015854:Up-Regulation; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
C408982:CPG-oligonucleotide; C106641:DEFB4A protein, human; D005229:Fatty Acids, Monounsaturated; D006684:HLA-DR Antigens; D007155:Immunologic Factors; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D000644:Quaternary Ammonium Compounds; D023083:beta-Defensins; D004247:DNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane