Enhanced cytokine secretion from primary macrophages due to Dectin-1 mediated uptake of CpG DNA/β-1,3-glucan complex.
Unmethylated CpG sequences (CpG DNA) can induce Th1 response and thus become a potential immunotherapeutic agent. A key step in the treatment is to transport CpG DNA to its receptor TLR9 located in the endocytosis pathway of target immune cells. For the effective transport, we prepared a novel complex from a β-1,3-glucan schizophyllan (SPG) and CpG DNA, and administered the complex to murine peritoneal macrophages that had been previously activated by thioglycollate and expressed a major β-1,3-glucan receptor Dectin-1 on the cellular surface. Flow cytometric analysis and microscopic observation showed that the complex was taken up by the macrophage through Dectin-1 mediated pathway. Indeed, ELISA demonstrated that IL-12 production was increased sigmoidally with increasing SPG/CpG DNA ratio in the complexation, and reached the maximum at the SPG-rich composition. In the present work, we describe a new approach to deliver CpG DNA to immune cells by use of a β-1,3-glucan/DNA complex.
Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
Jusaku
J
Minari
Shinichi
S
Mochizuki
Tsubasa
T
Matsuzaki
Yoshiyuki
Y
Adachi
Naohito
N
Ohno
Kazuo
K
Sakurai
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D004337:Drug Carriers / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D037181:Lectins, C-Type; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D012566:Sizofiran / Q000378:metabolism*; D000099181:Dectin-1
D016207:Cytokines; D004247:DNA; D004337:Drug Carriers; D018664:Interleukin-12; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012566:Sizofiran; D000099181:Dectin-1