Activation of microglia and astrocytes by CpG oligodeoxynucleotides.
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate cells of the immune system to secrete a variety of cytokines and chemokines. This function can be carried out by microglia and astrocytes in the CNS. To evaluate the effect of CpG ODN on microglia and astrocytes, purified cells were isolated and cultured in vitro. CpG ODN rapidly up-regulated their production of IL-1beta, IL-6, IL-12, TNFalpha, MIP-1alpha and/or MIP-1beta. In vivo, systemically administered CpG ODN up-regulated the expression of mRNA encoding cytokines and chemokines in normal mouse brain. These findings suggest that CpG ODN can directly activate immune cells of the CNS.
Takeshita
S
S
Section of Retroviral Immunology, Bldg 29A, Rm 3 D 10, Center for Biologics and Evaluation Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Takeshita
F
F
Haddad
D E
DE
Janabi
N
N
Klinman
D M
DM
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
C408982:CPG-oligonucleotide; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D016207:Cytokines; D007378:Interleukins; D019402:Macrophage Inflammatory Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha