CpG oligodeoxynucleotides induce murine macrophages to up-regulate chemokine mRNA expression.
Intramuscular injection of synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs trigger the rapid development of a local inflammatory response. In vitro studies demonstrate that macrophages exposed to CpG ODN up-regulate expression of mRNA encoding the chemokines MIP-1alpha, MIP-1beta, MIP-2, RANTES, JE/MCP-1, and IP-10. Within 6 h of in vivo administration, CpG ODN induce a significant increase in chemokine mRNA levels at the site of injection and draining lymph nodes. These chemokines may contribute to the migration and stimulation of inflammatory cells that contribute to the development of CpG ODN-induced immune responses.
Takeshita
S
S
Section of Retroviral Immunology, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Takeshita
F
F
Haddad
D E
DE
Ishii
K J
KJ
Klinman
D M
DM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C404915:Cxcl2 protein, mouse; D019402:Macrophage Inflammatory Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D007371:Interferon-gamma