CpG DNA induces cyclooxygenase-2 expression and prostaglandin production

Yongjin Chen; Juan Zhang; Steven A Moore; Zuhair K Ballas; Joseph P Portanova; Arthur M Krieg; Daniel J Berg

doi:10.1093/intimm/13.8.1013

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CpG DNA induces cyclooxygenase-2 expression and prostaglandin production

Journal article

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CpG DNA induces cyclooxygenase-2 expression and prostaglandin production

Yongjin Chen, Juan Zhang, Steven A Moore, Zuhair K Ballas, Joseph P Portanova, Arthur M Krieg and Daniel J Berg

International immunology, Vol.13(8), pp.1013-1020

08/2001

DOI: 10.1093/intimm/13.8.1013

PMID: 11470771

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Abstract

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-gamma secretion in vitro from CpG DNA-stimulated spleen cells. Moreover, selective COX-2 inhibition increased CpG DNA-induced IFN-gamma 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.

Details

Title: Subtitle: CpG DNA induces cyclooxygenase-2 expression and prostaglandin production
Creators: Yongjin Chen
Juan Zhang
Steven A Moore
Zuhair K Ballas
Joseph P Portanova
Arthur M Krieg
Daniel J Berg
Resource Type: Journal article
Publication Details: International immunology, Vol.13(8), pp.1013-1020
DOI: 10.1093/intimm/13.8.1013
PMID: 11470771
NLM abbreviation: Int Immunol
ISSN: 0953-8178
eISSN: 1460-2377
Language: English
Date published: 08/2001
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Immunology; Internal Medicine
Record Identifier: 9984047890302771

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