CpG-ODNs induces up-regulated expression of chemokine CCL9 in mouse macrophages and microglia.
Unmethylated CpG oligodeoxynucleotides (CpG-ODNs) interact with Toll-like receptor (TLR) 9 to activate macrophage/microglia in central nervous system (CNS). Here, we investigated the potential involvement of the chemokine CCL9 and its receptor CCR1 in the effects of CpG-ODNs on macrophage/microglial cells. CpG-ODNs enhanced the expression of TLR9 mRNA of RAW264.7 macrophage and BV2 microglia cells time dependently. The expression of CCL9 of macrophages/microglia showed different responsiveness upon stimulation with a variety of CpG-ODN sequences. The CpG-ODNs-mediated induction of CCL9 was TLR9/MyD88 dependent and associated with activation of stress kinases, particularly ERK, p38 MAPK and PI3K. The expression of CCR1 was also significantly increased by CpG-ODNs that increased CCL9 expression. These results reveal the potential involvement of CCL9 and CCR1 in regulation of macrophage and microglial cells by CpG-ODNs and may help improving our understanding about the role of the chemokine/chemokine receptor pairs in macrophage/microglia under physiologic and pathologic conditions.
Ravindran
C
C
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Cheng
Yung-Chih
YC
Liang
Shu-Mei
SM
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D007093:Imidazoles / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D054389:Receptors, CCR1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D016229:Amyloid beta-Peptides; C408982:CPG-oligonucleotide; C095218:Ccl9 protein, mouse; C515301:Ccr1 protein, mouse; D019742:Chemokines, CC; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D019402:Macrophage Inflammatory Proteins; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011725:Pyridines; D054389:Receptors, CCR1; D051217:Toll-Like Receptor 9; C075222:amyloid beta-protein (1-42); D002738:Chloroquine; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one