• BMB Reports
• /
• v.40 no.4
• /
• pp.486-493
• /
• 2007

Atopic dermatitis (AD) is a chronic inflammatory skin disease and the pathogenesis of AD is associated with the release of various cytokines/chemokines due to activated $Th_2$ immune responses. Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG dinucleotide in the context of particular base sequence (CpG motifs) are known to have the immunostimulatory activities in mice and to convert from Th2 to Th1 immune responses in AD. We aimed to investigate that CpG ODN, especially phosphodiester form, can stimulate the protective immunity in NC/Nga mice with AD. We isolated BMDCs from NC/Nga mice and then, cultured with GM-CSF and IL-4 for 6 days, and treated for 2 days by either phosphorothioate ODN or phosphodiester ODN. CpG ODN-treated DCs resulted in more production of IL-12. When CpG ODN-treated DCs were intravenously injected into the NC/Nga mice, the NC/Nga mice with CpG ODN-treated DCs showed significant improvement of AD symptoms and decrease of IgE level. Histopathologically, the NC/Nga mice skin with CpG ODN-treated DCs showed the decreased IL-4 and TARC expression comparing with non-injected mice. These results may suggest that phosphodiester CpG ODN-treated DCs might function as a potent adjuvant for AD in a mouse model.

• BMB Reports
• /
• v.54 no.2
• /
• pp.142-147
• /
• 2021

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG phosphorothioate (PS CpG-ODN) are known to decrease IgE synthesis in Th2 allergy responses. Nonetheless, the therapeutic role of PS CpG-ODN is limited due to cytotoxicity. Therefore, we developed a phosphodiester (PO) form of CpG-ODN (46O) with reduced toxicity but effective against allergies. In this study, we first compared the toxicity of 46O with CpG-ODNs containing a PS backbone (1826S). We also investigated the therapeutic efficacy and mechanism of 46O injected intravenously in a mouse model of ovalbumin (OVA)-induced atopic dermatitis (AD). To elucidate the mechanism of 46O underlying the inhibition of IgE production, IgE- and TGF-β-associated molecules were evaluated in CD40/IL-4- or LPS/IL-4-stimulated B cells. Our data showed that the treatment with 46O was associated with a lower hematological toxicity compared with 1826S. In addition, injection with 46O reduced erythema, epidermal thickness, and suppressed IgE and IL-4 synthesis in mice with OVA-induced AD. Additionally, 46O induced TGF-β production in LPS/IL-4-stimulated B cells via inhibition of Smad7, which suppressed IgE synthesis via interaction between Id2 and E2A. These findings suggest that enhanced TGF-β signaling is an effective treatment for IgE-mediated allergic conditions, and 46O may be safe and effective for treating allergic diseases such as AD and asthma.

• Journal of Dairy Science and Biotechnology
• /
• v.30 no.1
• /
• pp.31-36
• /
• 2012

Lactobacillus rhamnosus GG(ATCC 53103) is one of the best researched probiotic strains in the world. Studies in children have shown that Lactobacillus rhamnosus GG effectively prevents early atopic disease in patients with high risk. The active molecules associated with the immunostimulatory sequence and anti-allergy effects of L. rhamnosus GG have not yet been identified. Unmethylated CpG motifs in bacterial DNA have a mitogenic effect in mouse immune cells, CpG-containing ISS oligodeoxynucleotides are potent Th1 adjuvants, effective in both preventing and reversing Th2-biased immune deviation in allergy models. The genomic DNA of L. rhamnosus GG is a potent inducer of murine B cell and dendritic cell immunoactivation. In L. rhamnosus GG genomic DNA, ID35 shows high activity in ISS assays in both mice and humans. The effects of ID35 result from a unique TTTCGTT motif located at its 5'-end, and its effects are comparable with murine prototype CpG 1826. L. rhamnosus GG is known to secrete proteinaceous pili encoded by the spaCBA gene cluster. The presence of pili structures may be essential for its adhesion to human intestinal mucus, explaining the prolonged duration of intestinal residence of this bacterium, compared to that of non-piliated lactobacilli.

• Proceedings of the Korean Society of Sericultural Science Conference
• /
• 2002.10a
• /
• pp.58-58
• /
• 2002

No Abstract, See Full Text

• Journal of Life Science
• /
• v.27 no.4
• /
• pp.482-499
• /
• 2017

Allergic diseases have increased over the past several decade worldwide including developing countries. Allergic inflammatory responses are caused by Th (T helper)2 immune responses, triggered by allergen ingestion by antigen presenting cells such as dendritic cells (DCs). Intestinal microorganisms control the metabolism and physiological functions of the host, contribute to early immune system maturation during the early life, and homeostasis and epithelial integrity during life. Bifidobacteria have strain-specific immunostimulatory properties in the Th1/Th2 balance, inhibit TSLP (thymic stromal lymphopoietin) and IgE expression, and promote Flg (Filaggrin) and FoxP3 (Treg) expression to alleviate allergies. In addition, unmethylated CpG motif ODN (oligodeoxynucleotides) is recognized by TLR (toll-like receptors)9 of B cells and plasmacytoid dendritic cells (pDCs) to induce innate and adaptive immune responses, while the butyrate produced by Clostridium butyricum activates the GPR (G-protein coupled receptors)109a signaling pathway to induce the expression of anti-inflammatory gene of pDCs, and directly stimulates the proliferation of thymically derived regulatory T (tTreg) cells through the activation of GPR43 or inhibits the activity of HADC (histone deacetylase) to differentiate naive $CD4^+$ T cells into pTreg cells through the histone H3 acetylation of Foxp3 gene intronic enhancer.

• Journal of Ginseng Research
• /
• v.31 no.4
• /
• pp.181-190
• /
• 2007

Compound K (CK), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. In this study, we isolated the CK rich fractions (CKRF) from Korean Red Ginseng and investigated the regulation of CKRF-mediated inflammatory signaling during Toll-like receptor (TLR)-mediated cellular activation. Among various TLR ligands, CKRF considerably abrogated TLR4- or TLR9-induced inflammatory signaling. Both LPS and CpG-containing oligodeoxynucleotides (CpG-ODN) stimulation rapidly activates mitogen-activated protein kinases [MAPKs; extracellular signal-regulated kinases 1/2 and p38], NF-${\kappa}B$, and expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$, and interleukin-6 in murine bone marrow-derived macrophages (BMDMs) in a time- and dose-dependent manner. Of interest, pre-treatment of CKRF in either LPS/TLR4- or CpG-ODN/TLR9-stimulated macrophages substantially attenuated the LPS-induced inflammatory cytokine production and mRNA expressions, as well as MAPK and NF-${\kappa}B$ activation. To our knowledge, this is the first description of the inhibitory roles for CKRF in TLR4- or TLR9-associated signaling in BMDMs. Collectively, these results demonstrate that CKRF specifically modulates distinct TLR4 and TLR9-mediated inflammatory responses, and further studies are urgently needed for their in vivo roles for potential therapeutic uses, such as in systemic inflammatory syndromes.