International Immunology, Vol. 13, No. 8, 1013-1020,
August 2001
© 2001 Japanese Society for Immunology
CpG DNA induces cyclooxygenase-2 expression and prostaglandin production
1 Departments of Internal Medicine and
2 Department of Pathology, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
3 Department of Veterans Affairs Medical Center, Iowa City, IA 52242, USA
4 Department of Inflammatory Disease Research, Pharmacia, St Louis, MO 63198, USA
Correspondence to: D. J. Berg
Unmethylated CpG motifs found in bacterial DNA are potent activators of the innate and acquired immune systems, and rapidly induce the production of proinflammatory cytokines. We hypothesized that CpG DNA may also elicit the production of prostaglandins (PG), which are central lipid mediators of the immune and inflammatory response. To test our hypothesis, we stimulated murine spleen cells and RAW 264.7 murine macrophage cells with CpG DNA and assessed the effects on the PG synthesis pathway. Compared to control, DNA-containing CpG motifs induced >5-fold increase in PGE
2
production and rapidly up-regulated cyclooxygenase-2 (COX-2) at both the mRNA and protein level. CpG DNA was an extremely strong inducer of COX-2 as concentrations as low as 3 ng/ml induced COX-2 protein expression. The CpG DNA-induced PGE
2
down-regulated the immune response elicited by CpG. Blockade of PGE
2
production with selective COX-2 inhibitors or neutralizing anti-PGE
2
antibody markedly enhanced IFN-
secretion
in vitro
from CpG DNA-stimulated spleen cells. Moreover, selective COX-2 inhibition increased CpG DNA-induced IFN- secretion
in vivo
. Inhibition of COX-2 also increased CpG DNA-induced lytic activity of NK cells. Taken together, these data indicate that DNA containing CpG motifs is a potent inducer of COX-2 and PGE
2
production. CpG-induced PG may subsequently down-regulate the immune and inflammatory responses elicited by the CpG DNA.
Keywords: CpG DNA, cyclooxygenase, cytokines, inflammatory mediators, prostaglandins
Transmitting editor: J. Allison
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