• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.12-28
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• 2001

Background and Object : Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the $T_{H1}$-type immune response and down-regulate the $T_{H2}$-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperresponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. Materials and Methods : 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovalbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl) on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-${\gamma}$($T_{H1}$-type cytokine) and IL-4($T_{H2}$-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. Results : In the BALF of the CpG group, the IFN-${\gamma}$ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5AC gene expression was observed between the CpG group and the AC group. Conclusion : ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the $T_{H1}$-type immune response with the down-regulation of the $T_{H2}$-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

• Fisheries and Aquatic Sciences
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• v.10 no.1
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• pp.1-7
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• 2007

The induction of cellular and humoral immunity and cytokine gene expression by synthetic CpG oligodexoynucleotides (CpG-ODNs) has not been investigated systematically in olive flounder Paralichthys olivaceus in vivo. We optimized the proper concentration of CpG-ODNs using an in vitro assay for the superoxide anion $(O_2^-)$. CpG-ODNs induced $O_2^-$ and nitric oxide (NO) production, lysozyme activity, and the proinflammatory cytokine gene expression of $IL-1{\beta}$ and $TNF-{\alpha}$ in olive flounder significantly in vivo, whereas non-CpG-ODNs did not produce these effects or produced them to a lesser extent. This implied that CpG-ODNs could stimulate cellular and humoral immunity and cytokine gene expression in olive flounder. This is the first evidence of NO production and the first study on the mRNA expression of the proinflammatory cytokine genes $IL-1{\beta}$ and $TNF-{\alpha}$ in olive flounder in response to CpG-ODNs. Comparison of the variation in NO production and lysozyme activity to that of other studies led us to postulate that a group-specific difference exists in the immune responses of olive flounder against CpG-ODNs. Furthermore, the detailed immunostimulatory spectrum of CpG-ODNs in olive flounder could be a useful index with which to analyze the effect of CpG-ODNs against the challenge test prior to field applications.

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

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

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