• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.41-49
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• 2009

Soeumin-Googwihyangso-san(SGGHSS) has been used for the prevention or treatment of Soeumin-allergic rhinitis. This study was performed to demonstrate anti-allergic and anti-inflamatory effects of SGGHSS methanol extract in HMC cell lines and activated mouse B cells and CD4+ T cells. SGGHSS inhibited the production of TNF-$\alpha$ in PMA plus A23187 activated HMC-1 cells but not that of IL-6, as measured by ELISA. SGGHSS inhibited the expression of CD23 and surface IgE in B cells as determined by flowcytometry. It also inhibited secretion of IFN-$\gamma$ and IgG1, the Th1 related IgG type, but increased that of IL-4 in anti-CD40 and IL-4 treated B cells as measured by ELISA. As for Th cell differentiation, SGGHSS did not much affect IL-4 or IFN-$\gamma$. Taken together, our data showed that SGGHSS exerted an anti-inflammtory effect by inhibiting TNF-$\alpha$ in mast cells and has anti-allergic activity not via inhibition of CD4+ T cell, but via inhibition of B cells. These results suggest some evidence that SGGHSS can be applied to allergic disease.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.40-54
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• 2006

Objective: This study aimed to identify the different effects of GMCSBHT water-extract and ethanol-extract on Th1/Th2 differentiation by monitoring Th1/Th2 specific cytokine secretion patterns and the transcriptional activities of T-bet, GATA-3, c-maf, $INF{\gamma}$ and IL-4. Materials and Methods: Spleen cells from eight week-old BALB/c mice were cultured in GMCSBHT extracts containing medium without activation for 24 hours and with activation for 48 hours. CD4+ T cells were isolated and mRNA expression levels of $INF{\gamma}$, IL-4, T-bet, GATA-3, c-maf by RT-PCR and secretion cytokines levels of $IFN{\gamma}$, IL-4 by ELISA were analyzed. Results: GMCSBHT extracts didn't have mitogenic effects on the unstimulated CD4+ T cells. In Th1 skewed condition, GMCSBAHT water extract had no significant effects on mRNA expression levels of $IFN{\gamma}$, T-bet and c-maf, but inhibited mRNA expression levels of IL-4, GATA-3. It showed significantly increased secretion cytokine levels of $IFN{\gamma}$, but had no significant effect on secretion cytokine levels of IL-4. In Th2 skewed condition, GMCSBHT ethanol extract inhibited mRNA expression levels of $INF{\gamma}$, IL-4, GATA-3 and c-maf significantly, but had no significant effects on mRNA expression levels of T-bet. It had no significant effects on secretion cytokine levels of $INF{\gamma}$, but showed remarkable inhibitory effects on secretion cytokine levels of IL-4. Conclusion: Results suggest that on Th1/Th2 deviation, GMCSBHT water extract has both amplifying effects on Th1 differentiation and inhibitory effects on Th2, but GMCSBHT ethanol extract has stronger inhibitory effects on Th2 differentiation than on Th1.

• IMMUNE NETWORK
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• v.14 no.1
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• pp.30-37
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• 2014

Collaboration of TLR and non-TLR pathways in innate immune cells, which acts in concert for the induction of inflammatory cytokines, can mount a specific adaptive immune response tailored to a pathogen. Here, we show that murine DC produced increased IL-23 and IL-6 when they were treated with LPS together with curdlan that activates TLR4 and dectin-1, respectively. We also found that the induction of the inflammatory cytokine production by LPS and curdlan requires activation of IKK. However, the same treatment did not induce DC to produce a sufficient amount of TGF-${\beta}$. As a result, the conditioned media from DC treated with LPS and curdlan was not able to direct $CD4^+$ T cells to Th17 cells. Addition of TGF-${\beta}$ but not IL-6 or IL-$1{\beta}$ was able to promote IL-17 production from $CD4^+$ T cells. Our results showed that although signaling mediated by LPS together with curdlan is a potent stimulator of DC to secrete many pro-inflammatory cytokines, TGF-${\beta}$ production is a limiting factor for promoting Th17 immunity.

• BMB Reports
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• v.47 no.2
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• pp.115-120
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• 2014

In this study, we show that Mycobacterium avium subsp. paratuberculosis MAP1305 induces the maturation of bone marrow-derived dendritic cells (BMDCs), a representative antigen presenting cell (APC). MAP1305 protein induces DC maturation and the production of pro-inflammatory cytokines (Interleukin (IL)-6), tumor necrosis factor (TNF)-${\alpha}$, and IL-$1{\beta}$) through Toll like receptor-4 (TLR-4) signaling by directly binding with TLR4. MAP1305 activates the phosphorylation of MAPKs, such as ERK, p38MAPK, and JNK, which is essential for DC maturation. Furthermore, MAP1305-treated DCs transform naive T cells to polarized $CD4^+$ and $CD8^+$ T cells, thus indicating a key role for this protein in the Th1 polarization of the resulting immune response. Taken together, M. avium subsp. paratuberculosis MAP1305 is important for the regulation of innate immune response through DC-mediated proliferation of $CD4^+$ and $CD8^+$ T cells.

• The Journal of Pediatrics of Korean Medicine
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• v.32 no.2
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• pp.1-10
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• 2018

Objectives This study investigated the effects of Hataedock treatment with Douchi on induction of allergic rhinitis in obese induced NC/Nga mice. Methods NC/Nga mice were divided into control group (Ctrl), allergic rhinitis induced obese mice group (ARE), and allergic rhinitis induced obese mice group with Douchi Hataedock treatment (FGT). The 3-week-old mice of the FGT group were given one 10 mg/kg dose of Douchi Hataedock extract and sensitized with allergic antigens at weeks 4, 5, and 6. After 1 week of final sensitization, allergic rhinitis was induced primarily in mice nasal cavities for five days. After one week of the completion with the first induction, the second induction was introduced by the same method. After 1 week, few samples of the nasal mucosal tissues of each group were prepared. The factor of Th2 differentiation and inflammation control such that IL-4, STAT6, CD40, $Fc{\varepsilon}RI$, substance P, MMP-9, $NF-{\kappa}B$ p65, p-IkB, iNOS and COX-2 were observed by immunohistochemistry. Also, the difference in nasal mucosal injury was observed by histochemical method (PAS staining). Results The FGT group showed that reduced IL-4 production, STAT6 expression and CD40 expression by regulating excessive Th2 differentiation. Also, production of substance P and MMP-9 and activity of $Fc{\varepsilon}RI$ in mast cells were decreased. Inhibition of $NF-{\kappa}B$ p65 activity was induced by inhibition of p-IkB, and the production of inflammatory enzymes iNOS and COX-2 were decreased. In addition, the damage of intramural respiratory epithelium was low and excessive mucin secretion in goblet cells was low. Conclusions This study confirmed the possibility of controlling the allergic rhinitis in obese children who are expected to have an overactive inflammation.

• BMB Reports
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• v.47 no.9
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• pp.512-517
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• 2014

In this study, we showed that Mycobacterium abscessus MAB2560 induces the maturation of dendritic cells (DCs), which are representative antigen-presenting cells (APCs). M. abscessus MAB2560 stimulate the production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-${\alpha}$, IL-$1{\beta}$, and IL-12p70] and reduce the endocytic capacity and maturation of DCs. Using $TLR4^{-/-}$ DCs, we found that MAB2560 mediated DC maturation via Toll-like receptor 4 (TLR4). MAB2560 also activated the MAPK signaling pathway, which was essential for DC maturation. Furthermore, MAB2560-treated DCs induced the transformation of $na\ddot{i}ve$ T cells to polarized $CD4^+$ and $CD8^+$ T cells, which would be crucial for Th1 polarization of the immune response. Taken together, our results indicate that MAB2560 could potentially regulate the host immune response to M. abscessus and may have critical implications for the manipulation of DC functions for developing DC-based immunotherapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.69-74
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• 2005

In Oriental medicine the primordial Qi and the defensive Qi are considered as important for immunity. Therefore it is anticipated that the improvement of the primordial Qi and the defensive Qi can enhance the ability of immune cells. This experiment was conducted to investigate how Ginseng Radix, Astragali Radix, Atractylodis Rhizoma Alba, Glycyrrhizae Radix, representative of Qi tonifying herbs, affect the immune system in terms of controlling and balancing immune cells. Using the MTS assay, increased proliferations were observed from herbal treated cells, among which Gins-eng showed the highest proliferation. When splenocytes were activated with anti-CD3 plus herbal extracts, levels of IFN-g and IL-4 were increased but those of IL-2 showed little change compared with the control cells. Levels of IL-2, IFN-g and IL-4 were increased in purified CD4 T cells when activated with anti-CD3/anti-CD28 but at $100\;{\mu}g/ml$ of Astragali and Atractylodis, levels of IL-2 were decreased by 11% and 42%, respectively and those of IFN-g were decreased by 55% and 12%, respectively. Under Th1/Th2 polarizing conditions, levels of IFN-g in Th1 cells treated with herbal extracts were all decreased but when it comes to IL-4, its levels were increased in Ginseng and Glycyrrhizae treated cells but decreased in Astragali and Atractylodis treated cells. Taken together, the data show that compared with other qi tonifying herbs, Ginseng and Glycyrrhizae have a tendency to favor Th2 cell differentiation in vitro.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1467-1476
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• 2006

This study was to evaluate the effect of Bulhwangeumjeonggi-san (BS) on mouse Th1 and Th2 cells' differentiation and ovalbumin (OVA)-induced allergic inflammation. The proliferation of mouse CD4 T cells and the secretion of Th1/Th2 cytokines under the influence of BS extract were measured as well as the amount ${\beta}$-hexosaminidase in RBL-wH3 cells and the levels of TNF-${\alpha}$ and IL-6 secretion in Raw264.7 cells. BALB/c mice were orally administered with BS extract and simultaneously inoculated with OVA to induce allergic reaction and measure the level of total lgE, OVA-specific lgE and the production of IFN- g, IL-4, IL-5 by the spleen cells. When mouse CD4- T cell were stimulated with anti-CD3 and anti-CD28 for 48 hours in various concentrations of BS extract, it increased proliferation of CD4 cells by 14% in 50 ${\mu}g/m{\ell}$ concentration but it showed an inhibition in higher concentrations. CD4 T cells under Th1/Th2 polarizing conditions for 3 days with BS resulted in mild decrease of IFN- g in Th1 cells and mild increase of IL-4 in Th2 cell at 50 ${\mu}g/m{\ell}$ but the level of IL-4 decreased by 18% at 100 ${\mu}g/m{\ell}$. BS extract had a dose-dependent inhibitory effect on antigen-induced release of ${\beta}$-hexosaminidase in RBL-2H3 cells. Treatment of BS extract on LPS stimulated Raw 264.7 cells showed dose-dependent decrease in TNF-${\alpha}$ production. Oral administration of BS extract on OVA-induced allergic mice showed an inhibitory effect on the levels of total serum lgE and OVA-specific lgE by 50% and 55%, respectively. Culture of spleen cells with OVA resulted in significant increase of IFN- g by 25% and significant decrease of IL-4 and IL-5 by 53%, and 38%, respectively. The results show that BS does not strongly induce mouse T cells to transform into Th1 or Th2 but it has an anti-allergic effect in vitro, and that it also corrects the unbalance between the reactions of Th cells in allergic diseases.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.282-290
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• 2020

Background: Ginseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In this project, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC and related immune regulation mechanisms. Methods: Ginseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharide portion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper cell differentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cell cycle and apoptotic investigation. Results: GBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation, inhibited CD4⁺IFN-γ⁺ cell (Th1) differentiation, and decreased CD4⁺FoxP3⁺ cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggesting that it has an important role in antiinflammation, whereas Treg cells hinder the body's immune response against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at various degrees, remarkably enhanced the anticancer activities of 5-fluorouracil. Conclusion: Data from this project suggested that Asian ginseng berry potentially has clinical utility in managing enteric inflammation and suppressing CRC through immunomodulation mechanisms.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.844-852
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• 2006

This study was to evaluate the effect of Yeongyupaedog-san (YGPDS) on mouse Thl and Th2 cells' differentiation and ovalbumin (OVA)-induced allergic inflammation. The proliferation of mouse CD4 T cells and the secretion of Th1/Th2 cytokines under the influence of YGPDS extract were measured as well as the amount of ${\beta}-hexosaminidase$ in RBL-2H3 cells and the levels of $TNF-{\alpha}$ and 1L-6 secretion in Raw264.7 cells. BALB/c mice were orally administered with YGPDS extract and simultaneously inoculated with OVA to induce allergic reaction and measure the level of total IgE, OVA-specific IgE and the production of IFN- g, IL-4, IL-5 by the spleen cells. When mouse CD4 T cell were stimulated with anti-CD3 and anti-CD28 for 48 hours in various concentrations of YGPDS extract, it increased proliferation of CD4 cells by 11% in $100\;{\mu}g/^{ml}$ concentration but it showed an inhibition by 37% at $200\;{\mu}g/^{ml}$ CD4 T cells under Th1/Th2 polarizing conditions for 3 days with YGPDS resulted in mild decrease of IFN- g in Thl cells and significant decrease of IL-4 in Th2 cells at $500\;{\mu}g/^{ml}\;and\;100\;{\mu}g/^{ml}$ by 18% and 21%, respectively. YGPDS extract had a dose-dependent inhibitory effect on antigen-induced release of ${\beta}-hexosaminidase$ in RBL-2H3 cells. Treatment of YGPDS extract on LPS stimulated Raw 264.7 cells showed dose-dependent decrease in TNF-n production. Oral administration of YGPDS extract on OVA-induced allergic mice showed an inhibitory effect on the levels of total serum IgE and OVA-specific IgE by 25% and 34% , respectively. Culture of spleen cells with OVA resulted in significant increase of IFN- g by 44% and significant decrease of IL-4 and IL-5 by 56%, and 24%, respectively. The results show that YGPDS does not strongly induce mouse T cells to transform into Thl or Th2 but it has an anti-allergic effect in vitro, and that it also corrects the unbalance between the reactions of Th cells in allergic diseases.