title: CpG oligodeoxynucleotides induce expression of proinflammatory cytokines and chemokines in astrocytes: the role of c-Jun N-terminal kinase in CpG ODN-mediated NF-kappaB activation.
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 IkappaB 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-kappaB signaling.
authors.affiliation: LG Life Sciences Ltd., Daejon, South Korea.
authors.forename: Soojin
authors.initials: S
authors.lastname: Lee
authors.forename: Jinpyo
authors.initials: J
authors.lastname: Hong
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Seog Bae
authors.initials: SB
authors.lastname: Oh
authors.forename: Kyungpyo
authors.initials: K
authors.lastname: Park
authors.forename: Joong Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.forename: Sung Joong
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
chemical_list: C408982:CPG-oligonucleotide; D018925:Chemokines; D016207:Cytokines; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases