Inhibitory oligodeoxynucleotides (ODNs), which are capable of blocking CpG-induced inflammation, have been anticipated to be beneficial therapeutic agents for autoimmune diseases. In this study, we show that GpC ODN, which inverted the cytosine guanine sequence of CpG motif to guanine cytosine sequence, is an inhibitory ODN. The inhibitory effects of GpC ODN on CpG ODN-induced immune activation...

Two distinct types of CpG oligodeoxynucleotide (ODN) have been identified that differ in their capacity to stimulate antigen-presenting cells: CpG-A induces high amounts of interferon-alpha (IFN-alpha) and IFN-beta in plasmacytoid dendritic cells (PDCs), whereas CpG-B induces PDC maturation and is a potent activator of B cells but stimulates only small amounts of IFN-alpha and IFN-beta. Here we...

Nucleic acid cellular uptake into endosomes is critical in eliciting nucleotide-sensing toll-like receptors (TLRs) innate immune responses. ADP-ribosylation factor 6 (ARF6) is a member of the Ras superfamily, which is critical to a wide variety of cellular events including endocytosis. Our previous report indicated that ARF6 plays a critical role in CpG ODN/TLR9-mediated responses. Here, we fur...

The role of NKT cells on antitumor activity of CpG oligodeoxynucleotides (ODNs) was evaluated by peritumoral injections of CpG-ODNs in s.c. melanoma-bearing mice of strains differing in the number of NKT cells (athymic nude mice, recombination-activating gene(-/-)/transgenic V(alpha)14/Vbeta8.2 mice that generate NKT cells; J(alpha)281(-/-) mice and CD1(-/-) mice, which both have a strongly red...

Unmethylated cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs) exhibit potent immunostimulating activity by binding with Toll-like receptor 9 (TLR9) expressed on antigen-presenting cells. Here, we show that CpG-ODN encapsulated in cationic liposomes (CpG-liposomes) improves its incorporation into CD11c(+) dendritic cells (DCs) and induces enhanced serum interleukin (IL)-12 leve...

CpG-DNA and its related synthetic CpG oligodeoxynucleotides (CpG-ODNs) play an important role in immune cell survival. It has been suggested that Akt is one of the CpG-DNA-responsive serine/threonine kinases; however, the target protein of CpG-DNA that leads to Akt activation has not been elucidated. Here, we report that ex vivo stimulation of bone marrow-derived macrophages (BMDMs) from mice l...

CpG oligodeoxynucleotides (CpG-ODNs) affect innate and adaptive immune responses, including antigen presentation, costimulatory molecule expression, dendritic cell maturation, and induction of cytokines enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). We conducted a phase 1 study evaluating 4 dose levels of a CpG-ODN (1018 ISS) with rituximab in 20 patients with relapsed non-Hodg...

PURPOSE CpG oligodeoxynucleotides (ODNs) are synthetic DNA sequences that mimic bacterial DNA and have potent immunostimulatory effects on dendritic cells (DCs), B cells, and natural killer cells. To evaluate CpG ODN antitumor effects against solid tumors, we used an orthotopic murine model of embryonal rhabdomyosarcoma. EXPERIMENTAL DESIGN The systemic administration of CpG 2006 was tested b...

Cytosine-guanine oligodeoxynucleotide (CpG ODN) motifs of bacterial DNA are recognized through toll-like receptor 9 (TLR9) and are potent activators of innate immunity. However, the interaction between TLR9 and CpG ODN in aquatic species has not been well characterized. Hence, cobia TLR9 isoform B (RCTLR9B) was cloned and its expression and induction in intestine were investigated. RCTLR9B cDNA...