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CpG oligodeoxynucleotides induce expression of proinflammatory cytokines and chemokines in astrocytes: the role of c-Jun N-terminal kinase in CpG ODN-mediated NF-κB activation

Cited 36 time in Web of Science Cited 34 time in Scopus
Authors
Lee, Soojin; Hong, Jinpyo; Choi, Se-Young; Oh, Seog Bae; Park, Kyungpyo; Kim, Joong Soo; Karin, Michael; Lee, Sung Joong
Issue Date
2004-08
Publisher
Elsevier
Citation
Journal of Neuroimmunology 153, 50–63
Keywords
TLR9CpG ODNAstrocytesJNKNF-κB
Abstract
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate the cells of the innate immune system through a specific receptor called Toll-like receptor-9 (TLR9). It was reported that CpG ODN stimulation induces activation of astrocytes and microglia. However, the precise intracellular signaling pathways that lead to this glial cell activation have not been clearly elucidated. In this study, we found that CpG ODN induce mRNA expression of adhesion molecules and matrix metalloproteinase-9 (MMP-9), as well as proinflammatory cytokines and chemokines, in mouse astrocytes. CpG ODN stimulation in astrocytes induces the activation of IκB kinase (IKK) and c-Jun N-terminal kinase (JNK), whereas it inhibits the constitutive ERK1/2 activation. The abrogation of JNK activity using a pharmacological inhibitor showed that JNK activation is essential for the induction of cytokine and chemokine gene expression. This effect of JNK does not require the phosphorylation of c-Jun; rather, it works via the potentiation of NF-κB signaling.
ISSN
0165-5728
Language
English
URI
http://hdl.handle.net/10371/66621
DOI
https://doi.org/10.1016/j.jneuroim.2004.04.013
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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