CpG oligodeoxynucleotides directly induce CXCR3 chemokines in human B cells.
CpG oligodeoxynucleotides (CpG ODN) are known to elicit Th1 immune responses via TLR9. However, the precise mechanisms through which B cells are involved in this phenomenon are not fully understood. We investigated the effect of CpG ODN on the induction of Th1-chemoattractant CXCR3 chemokines, IP-10, Mig, and I-TAC, in B cells. Cells from the RPMI 8226 human B cell line and human peripheral B cells were stimulated with three distinct classes of CpG ODN. As a result, CXCR3 chemokines were strongly up-regulated by CpG-B and CpG-C, but only weakly by CpG-A. Though CXCR3 chemokines are known to be induced by IFNs, blocking mAbs against IFN receptors did not inhibit their induction by CpG-B. Induction of CXCR3 chemokines was blocked by two NF-kappaB inhibitors and a p38 inhibitor. These results strongly suggest that CXCR3 chemokines are directly induced by CpG ODN via NF-kappaB- and p38-dependent pathways in human B cells.
Kato
Atsushi
A
Department of Allergy and Immunology, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8567, Japan.
Ogasawara
Takahisa
T
Homma
Toshiki
T
Batchelor
Jonathan
J
Imai
Shosuke
S
Wakiguchi
Hiroshi
H
Saito
Hirohisa
H
Matsumoto
Kenji
K
D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D019743:Chemokines, CXC / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*
C408982:CPG-oligonucleotide; C515187:CXCR3 protein, human; D019743:Chemokines, CXC; D009838:Oligodeoxyribonucleotides; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine