title: Induction of immune activation by a novel immunomodulatory oligonucleotide without thymocyte apoptosis.
abstract: Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG DNA) can potently stimulate innate immunity. While the actions of CpG DNA resemble those of LPS, these molecules stimulate distinct Toll-like receptors as well as cell types. In a previous study, we showed that a CpG ODN could induce cytokine production but, unlike LPS, did not induce thymocyte apoptosis. In this study, we have further investigated these differences using as a model a second-generation immunostimulatory oligonucleotide called HYB2048. Following administration to normal BALB/c mice, HYB2048-induced IL-12 but not IL-6 production. Under conditions in which LPS induced thymocyte apoptosis, HYB2048 did not cause significant cell death and, furthermore, did not block apoptosis induced by LPS. The levels of corticosterone induced by HYB2048 were also significantly lower than those induced by LPS. This pattern of activation could distinguish CpG DNA from LPS in its effects on the immune system.
authors.affiliation: Division of Rheumatology and Department of Immunology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Weiwen
authors.initials: W
authors.lastname: Jiang
authors.forename: Charles F
authors.initials: CF
authors.lastname: Reich
authors.forename: Dong
authors.initials: D
authors.lastname: You
authors.forename: Ekamber
authors.initials: E
authors.lastname: Kandimalla
authors.forename: Sudhir
authors.initials: S
authors.lastname: Agrawal
authors.forename: David S
authors.initials: DS
authors.lastname: Pisetsky
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D003345:Corticosterone / Q000096:biosynthesis; D018899:CpG Islands; D005260:Female; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C408982:CPG-oligonucleotide; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12; D003345:Corticosterone