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International Immunology Advance Access published online on November 1, 2005
International Immunology, doi:10.1093/intimm/dxh345
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received April 13, 2005
Accepted October 4, 2005

Article

CpG oligodeoxynucleotides induce IL-8 expression in CD34+ cells via mitogen-activated protein kinase-dependent and NF-{kappa}B-independent pathways

Jung Mogg Kim 1*, Nam In Kim 1, Yu-Kyoung Oh 2, Young-Jeon Kim 3, Jeehee Youn 4, and Myung-Ju Ahn 5

1 Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Korea
2 School of Life Sciences and Biotechnology, Korea University, Korea
3 Department of Science, Joongbu University, Choongnam, Korea
4 Department of Anatomy and Cell Biology, Hanyang University College of Medicine, Seoul, Korea
5 Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea

* To whom correspondence should be addressed.
Jung Mogg Kim, E-mail: jungmogg{at}hanyang.ac.kr


  Abstract

To elucidate the role of Toll-like receptor 9 (TLR9) activation along with the intracellular signaling pathways triggered by CpG DNA in CD34+ cells, we investigated whether synthetic oligodeoxynucleotides (ODNs), containing unmethylated CpG motifs, could induce IL-8 expression in CD34+ cells through mitogen-activated protein kinase (MAPK) or nuclear factor-{kappa}B (NF-{kappa}B) pathway. We demonstrated evidence for the first time that CD34+ cells constitutively expressed TLR9. Exposure of the cells to CpG ODN resulted in a time- and dose-dependent increase of IL-8 expression, and activation of phosphorylated ERK1/2 and phosphorylated p38. In addition, CpG ODN stimulated AP-1, but not NF-{kappa}B, signals. Moreover, inhibitors of MAPK (U0126 and SB203580) significantly reduced the IL-8 production, while the inhibition of NF-{kappa}B (pyrrolidinedithiocarbamate and retrovirus containing dominant-negative I{kappa}B{alpha} plasmid) did not affect the IL-8 expression increased by CpG ODN. Moreover, co-stimulation with LPS and CpG synergistically up-regulates IL-8 in CD34+ cells. These results suggest that CpG DNA, acting on TLR9, activates CD34+ cells to express IL-8 through MAPK-dependent and NF-{kappa}B-independent pathways.

Keywords: AP-1; ERK1/2; p38; Toll-like receptor 9.
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