A polysaccharide carrier for immunostimulatory CpG DNAs to enhance cytokine secretion.
A beta-(1 --> 3)-d-glucan schizophyllan (SPG) forms a stoichiometric complex with some polynucleotides. This communication describes our attempt to apply the SPG complex to deliver CpG DNA to endosomes to enhance cytokine secretion. To increase cellular uptake, we introduced spermine, arginine-glycine-aspartic acid tripeptide, octaarginine, or cholesterol to the SPG side chain. The chemically modified SPG showed essentially no cytotoxicity. When CpG DNA complex made therefrom was exposed to macrophages, dramatic enhancement in the cytokine secretion was observed. It increased 5-10 times from the naked dose and 100 times from the background. This performance promises that SPG can be an excellent carrier for CpG DNA.
Mizu
Masami
M
Department of Chemical Processes and Environments, The University of Kitakyushu, 1-1 Hibikino, Wakamatu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
Koumoto
Kazuya
K
Anada
Takahisa
T
Matsumoto
Takahiro
T
Numata
Munenori
M
Shinkai
Seiji
S
Nagasaki
Takeshi
T
Sakurai
Kazuo
K
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D000818:Animals; D002240:Carbohydrate Sequence; D002460:Cell Line; D002784:Cholesterol / Q000008:administration & dosage / Q000737:chemistry; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D004247:DNA / Q000008:administration & dosage* / Q000276:immunology*; D004337:Drug Carriers; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry*; D012636:Secretory Rate / Q000187:drug effects; D012566:Sizofiran / Q000008:administration & dosage / Q000737:chemistry; D013096:Spermine / Q000008:administration & dosage / Q000737:chemistry
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004337:Drug Carriers; D008081:Liposomes; D009842:Oligopeptides; D011134:Polysaccharides; D013096:Spermine; C047981:arginyl-glycyl-aspartic acid; D012566:Sizofiran; D004247:DNA; D002784:Cholesterol