• The Korea Journal of Herbology
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• v.34 no.3
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• pp.9-17
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• 2019

Objectives : This study was performed to compare the effect of two Cudrania tricuspidata cultivars; Sancheong native (CT) and varieties in china(SCT) on immediate hypersensitivity of the anaphylactic type and Ova-induced allergic asthma mouse model by calculating serum cytokines and IgE. Methods : We investigated the free radical scavanging effect and quantify total phenol contents and total flavonoids of two Cudrania tricuspidata cultivars; Sancheong native(CT) and varieties in china(SCT). The sample was extracted by 80% EtOH. To induce the allergic asthma, in the control group and the CT group, mice of each group were sensitized intraperitoneally with ovalbumin (OVA) solution at the 1st, the 7th and the 14th day. After then, sensitization was performed by aerosol allergen challenges with 1% OVA solution intratracheally at the 21th, the 23th, 25th and the 27th day. At the 29th day, the mice were killed and the changes of interferon-${\gamma}$, interleukin-4, 5 and 10, total IgE and OVA-specific IgE in serum were checked. Results : CT inhibited compound 48/80-induced systemic anaphylaxis 90% with a dose of 100 mg/kg body weight at 1 hr before injection of compound 48/80. In the allergic asthma mouse model, IFN-${\gamma}$ was did not increased in the CT and SCT group than that in the control group. IL-4, IL-5, the total IgE and OVA-specific IgE were decreased in the CT group as compared with the control group and these results were statistically significant. Conclusions : Considering the above experimental results, this study showed that Sancheong native cultivar could reduce the allergic reaction.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.123-129
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• 2012

Objectives : Allergy has been described as an inflammatory with hypersensitivity resulting from seasonal or perennial responses to specific allergens. The root of Platycodon grandiflorum (Jacq.) A. DC.(Platycodi Radix; Campanulaceae) has been traditionally used to treat chronic diseases such as bronchitis, asthma, pulmonary tuberculosis, inflammation and hyperlipidemia. In this study, we examined the effect of 70% ethanol extract of Platycodi Radix (PR-E) on ovalbumin (OVA)-induced airway inflammation in mice. Methods : Mice were sensitized and challenged by OVA inhalation to induced chronic airway inflammation, and then were intragastrically administered PR-E extract at doses of 50 and 200 mg/kg/day from days 21 to 30 consecutively. The levels of allergic mediators such as histamine, OVA-specific immunoglobulin (Ig) E, and cytokines such as IL-4 and IFN-${\gamma}$ were measured in the sera of mice by ELISA. The histological change of lung tissue was observed by hematoxylin and eosin (H&E) staining. Results : PR-E extract significantly decreased the serum levels of histamine, OVA-specific IgE, and Th2 cytokine, IL-4 compared with those in the OVA-induced group. PE-E extract significantly increased the serum level of Th1 cytokine, IFN-${\gamma}$. Based on lung histopathological studies, inflammatory cell infiltration and mucus hypersecretion were inhibited by PE-E extract administration compared to that in the OVA-induced group. Conclusions : These findings indicate that PE-E extract may be useful as an adjuvant therapy for the treatment of bronchial asthma.

• Clinical and Experimental Pediatrics
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• v.45 no.7
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• pp.875-883
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• 2002

Purpose : Airways eosinophilia and increased IgE, characteristic features of asthma, result from a predominant Th2 response. In this study, we investigated the effect of CpG oligodeoxynucleotides (ODNs) on the inhibition of airways eosinophilia in mice with established airway inflammation. We also investigated the immunological mechanisms involved. Methods : Groups of BALB/c mice were sensitized intradermally with ovalbumin(OVA). At week 10, airway inflammation was induced by intranasal challenge of the mice with OVA. At week 14, the mice were challenged intranasally again with OVA in the presence and without the presence of CpG ODNs. Mice with saline administration served as negative controls. Bronchoalveolar lavage fluids(BALF) were obtained and eosinophils were counted. Th1 and Th2 cytokines in the spleen cell cultures were measured by ELISA. Serum OVA-specific IgE and IgG2a antibodies were also measured by ELISA. Results : BALF eosinophils were significantly inhibited in the CpG ODNs-treated mice(P<0.01). IgE and IgG2a levels increased significantly in both CpG ODNs-treated and untreated groups as compared to the negative control group; there was, however, no significant difference between the two groups four days after intranasal administration of CpG ODNs. Cytokine analysis revealed decreased production of IL-4, IL-5, and IL-13 and increased production of IL-12 in the CpG ODNs-treated group as compared to the untreated group. Interestingly, $IFN-{\gamma}$ levels were not upregulated in the CpG ODNs-treated group. Conclusion : CpG ODNs vaccination is a potentially useful approach for reversing airways eosinophilia in mice with established airways inflammation.

• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.543-552
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• 2004

Background : Airway remodeling of the asthmatic airway, the result of persistent inflammation in the bronchial wall, is associated with irreversible airway obstruction and the severity of asthma. Previous reports had represented that adminitering CpG-oligodeoxynucleotides (CpG-ODN) before sensitization or challenge by allergens inhibits the development of eosinophilic airway inflammation in a murine model of asthma, but the effects of CpG-ODNs on chronic inflammation and airway remodeling had not been characterized. To investigate the influence of CpG-ODNs on chronic inflammation and remodeling of the airway, we performed studies using a murine model of chronic allergen-induced asthma. Methods : Balb/C mice were sensitized to ovalbumin(OVA) and subsequently exposed to nebulized OVA by means of inhalation twice weekly for 7 weeks. CpG-ODNs($30{\mu}g$) was administered intraperitoneally at sensitization. After final inhalation, mice were evaluated for airway hyperresponsiveness, chronic airway inflammation and remodeling. Results : The mice exposed to chronic and recurrent airway challenge with OVA had persistent airway hyperresponsiveness, chronic inflammation and airway remodeling. Mice treated with CpG-ODNs exhibited decreased bronchial hyperresponsiveness, OVA-specific IgE, chronic inflammation and evidence of airway remodeling, including goblet cell hyperplasia and subepithelial fibrosis. Conclusion : CpG-ODNs was thought to prevent chronic inflammation and remodeling changes in a murine model of chronic asthma.

• The Journal of Pediatrics of Korean Medicine
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• v.32 no.3
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• pp.1-15
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• 2018

Objectives Alismatis Rhizoma has been known to suppress inflammation and allergic reaction. However, the cellular target of Alismatis Rhizoma and its mechanism of action remain unclear. This study was designed to examine the effect of Alismatis Rhizoma extract (ALC) on the RBL-2H3 mast cells in vitro and on the OVA/alum sensitized mice ex vivo. Methods In the study, RBL-2H3 mast cells were cultured in minimal essential medium (MEM) for 24 hours, and treated separately with cyclosporin A and varying doses of ALC, and then stimulated with Phorbol 12-myristate 13-acetate (PMA) (50 ng/ml) and Ionomycin ($0.5{\mu}M$). The levels of IL-13, IL-4 were measured by ELISA analysis. The mRNA levels of IL-4, IL-5, IL-6, IL-13, GM-CSF, $TNF-{\alpha}$ were analyzed with Real-time PCR. Also, manifestations of MAPKs transcription factors and $NF-{\kappa}B$ p65 translocation were analyzed by western blotting in vitro. Subsequently, for ex vivo experiment, we induced allergic inflammation on Balb/c mice by OVA/alum and administered ALC orally. And we measured serum OVA-specific IgE level and IL-4, IL-13 in the splenocyte culture supernatant by ELISA analysis. Results ALC was shown to suppress mRNA expression of IL-4, IL-5, IL-6, IL-13, GM-CSF, $TNF-{\alpha}$, and to inhibit the IL-13, IL-4 production. Also ALC reduced an activation of mast cells specific signal MAPKs transcription factors and $NF-{\kappa}B$ p65 from the western blot analysis in in vitro experiment. In ex vivo, ALC oral adminstration decreased the level of OVA-specific IgE in serum, and IL-4, IL-13 in the splenocyte culture supernatant. Conclusions ALC is shown to reduce inflammation and allergic response by suppressing Th2 cytokines through the regulation of transcription factors MAPKs and $NF-{\kappa}B$ p65 in mast cells. Administration of ALC suppressed OVA-specific IgE in ovalbumin allergy model through the inhibition of Th2 cytokine. In conclusion, ALC can be considered as an effective treatment for allergic diseases such as atopic dermatitis.

• Parasites, Hosts and Diseases
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• v.49 no.4
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• pp.373-380
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• 2011

We have reported that a 24 kDa protein (22U homologous; As22U) of Anisakis simplex larvae could elicit several Th2-related chemokine gene expressions in the intestinal epithelial cell line which means that As22U may play a role as an allergen. In order to determine the contribution of As22U to allergic reactions, we treated mice with 6 times intra-nasal application of recombinant As22U (rAs22U). In the group challenged with rAs22U and ovalbumin (OVA), the number of eosinophils in the bronchial alveolar lavage fluid (BALF) was significantly increased, as compared to the group receiving only OVA. In addition, mice treated with rAs22U and OVA showed significantly increased airway hyperresponsiveness. Thus, severe inflammation around the airway and immune cell recruitment was observed in mice treated with rAs22U plus OVA. The levels of IL-4, IL-5, and IL-13 cytokines in the BALF increased significantly after treatment with rAs22U and OVA. Similarly, the levels of anti-OVA specific lgE and lgG1 increased in mice treated with rAs22U and OVA, compared to those treated only with OVA. The Gro-${\alpha}$ (CXCL1) gene expression in mouse lung epithelial cells increased instantly after treatment with rAs22U, and allergy-specific chemokines eotaxin (CCL11) and thymus-and-activation-regulated-chemokine (CCL17) gene expressions significantly increased at 6 hr after treatment. In conclusion, rAs22U may induce airway allergic inflammation, as the result of enhanced Th2 and Th17 responses.

• Clinical and Experimental Pediatrics
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• v.54 no.9
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• pp.373-379
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• 2011

Purpose: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, $IgG_1$, and $IgG_{2a}$ levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. Results: In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific $IgG_1$ levels and increased serum $IgG_{2a}$ level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. Conclusion: Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.616-623
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• 2010

Three herbal formulas (Bangpungtongsung-san, Ohyaksungi-san, and Ojeok-san) for wind-cold and heat pain symptom were applied to investigate the immunological activities on antigen (Ag)-specific or Ag-non-specific immune responses in murine macrophage cell line (RAW 264.7) and ovalbumin (OVA)-immunized mice. This study was carried out in nitric oxide (NO) synthesis in RAW 264.7 cells and cellular proliferation in mouse splenocytes according to three herbal formulas. C57BL/6 mice were immunized intraperitonially with OVA/aluminium ($100\;{\mu}g/200\;{\mu}g$/mouse) on day 1, 8, and 15. Three herbal formulas were administrated to mice orally for 3 weeks from day 1. On day 22, OVA-, lipopolysaccharide (LPS)-, and concanavalin A (Con A)-stimulated splenocyte proliferation and antibodies (OVA-specific antibodies of the IgG, lgG1, and total IgM classes) in plasma were measured. Ohyaksungi-san increased NO synthesis in RAW 264.7 cells. Ojeok-san and Ohyaksungi-san significantly enhanced cellular proliferation by LPS and Con A in splenocytes from OVA-immunized mice (p<0.001). Three herbal formulas for wind-cold and heat pain symptom also significantly enhanced plasma OVA-specific IgG, IgG1, and total IgM levels compared with the OVA/Alum group. These results suggested that three herbal formulas for wind-cold and heat pain symptom could be used as stimulator of immune response.

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1210-1223
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• 2018

Background/Aims: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. Methods: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. Results: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. Conclusions: These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

• The Journal of Pediatrics of Korean Medicine
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• v.32 no.4
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• pp.71-86
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• 2018

Objectives The purpose of this study is to investigate the effects of Gardenia jasminoides for. grandiflora extracts' (GAJ) anti-inflammatory effect on RBL-2H3 mast cells and OVA/alum-sensitized mice. Methods In this study, IL-4 and IL-13 production was measured via ELISA analysis, and mRNA expressions of GM-CSF, IL-4, IL-5, $TNF-{\alpha}$, IL-6 were analyzed by real-time PCR. In addition, MAPKs and $NF-{\kappa}B$ p65 transcription factors were examined using western blotting, and ELISA was used to understand IgE, IL-4, and IL-13 production in ovalbumin-allergic mice in in vitro study. Results As a result of this study, 1. GAJ were observed to suppress the mRNA expression of GM-CSF, IL-4, IL-13, IL-5, $TNF-{\alpha}$, IL-6 in comparison to PMA 50 ng/ml, ionomycin $0.5{\mu}M$ (PI) control group. 2. GAJ also inhibited the IL-4, IL-13 production in comparison to PI control group. 3. Western blot analysis showed decrease on the expression of mast-cell-specific transcription factors, including MAKPs (ERK, JNK, p38) and $NF-{\kappa}B$ p65. 4. Orally-administered GAJ group in OVA/alum induced Balb/c mice showed decreased level of OVA-specific IgE in the serum. This group also has shown decreased the level of IL-4, IL-13 in the splenocyte culture supernatant. Conclusions Obtained results suggest that GAJ may regulate the allergic inflammation by transcription factors MAKPs (ERK, JNK, p38) and $NF-{\kappa}B$ p65 causing inhibition of Th2 cytokines in mast cells and OVA/alum-sensitized mice.