• The Korean Journal of Physiology and Pharmacology
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• v.23 no.4
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• pp.251-261
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• 2019

Allergic asthma, is a common chronic inflammatory disease of the airway presenting with airway hyperresponsiveness and airway remodelling. T helper cells-derived cytokines are critically associated with asthma pathogenesis. Janus kinase-signal transduction and activation of transcription (JAK/STAT) signaling is found to be involved in asthma. Magnolol is a plant-derived bioactive compound with several pharmacological effects. The study aimed to assess the effects of magnolol in ovalbumin (OVA)-induced asthmatic model. BALB/c mice were sensitized and challenged with OVA. Magnolol (12.5, 25, or 50 mg/kg body weight) was administered to separate groups of animals. Dexamethasone was used as the positive control. Cellular infiltration into the bronchoalveolar lavage fluid (BALF) were reduced on magnolol treatment. The levels of Th2 and Th17 cytokines were reduced with noticeably raised levels of interferon gamma. Lung function was improved effectively along with restoration of bronchial tissue architecture. OVA-specific immunoglobulin E levels in serum and BALF were decreased by magnolol. Magnolol reduced Th17 cell population and effectively modulated the JAK-STAT and Notch 1 signaling. The results suggest the promising use of magnolol in therapy for allergic asthma.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.481-491
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• 2018

Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects. We investigated the ability of rutin to modulate T-cells and inhibit inflammation in experimentally-induced asthma in cigarette smoke exposed mice. Separate groups of neonatal mice were exposed to CS for 10 days from post-natal days 2 to 11. After 2 weeks, the mice were sensitized and challenged with ovalbumin (OVA). Treatment group were given rutin (37.5 or 75 mg/kg body weight) during OVA sensitization and challenge. Rutin treatment was found to significantly inhibit cellular infiltration in the airways and Th2 and Th17 cytokine levels as well. Flow cytometry revealed effectively raised $CD4^+CD25^+Fox3^+$ Treg cells and supressed Th17 cell population on rutin treatment. Airway hyper-responsiveness observed following CS and OVA challenge were inhibited by rutin. $NF-{\kappa}B$ and iNOS, chief regulators of inflammatory responses robustly activated by CS and OVA were down-regulated by rutin. Rutin also inhibited the expression of matrix metalloproteinase 9, thereby aiding in prevention of airway remodelling in asthma thereby revealing to be a potent candidate in asthma therapy.

• Journal of Microbiology and Biotechnology
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• v.32 no.6
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• pp.709-717
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• 2022

Allergic rhinitis (AR), one of the most common inflammatory diseases, is caused by immunoglobulin E (IgE)-mediated reactions against inhaled allergens. AR involves mucosal inflammation driven by type 2 helper T (Th2) cells. Previously, it was shown that the Streptococcus pneumoniae pep27 mutant (Δpep27) could prevent and treat allergic asthma by reducing Th2 responses. However, the underlying mechanism of Δpep27 immunization in AR remains undetermined. Here, we investigated the role of Δpep27 immunization in the development and progression of AR and elucidated potential mechanisms. In an ovalbumin (OVA)-induced AR mice model, Δpep27 alleviated allergic symptoms (frequency of sneezing and rubbing) and reduced TLR2 and TLR4 expression, Th2 cytokines, and eosinophil infiltration in the nasal mucosa. Mechanistically, Δpep27 reduced the activation of the NLRP3 inflammasome in the nasal mucosa by down-regulating the Toll-like receptor signaling pathway. In conclusion, Δpep27 seems to alleviate TLR signaling and NLRP3 inflammasome activation to subsequently prevent AR.

• The Journal of Pediatrics of Korean Medicine
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• v.36 no.1
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• pp.57-64
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• 2022

Objectives The purpose of this study is to confirm the regulate effect of T helper (Th) 2 differentiation that Sabaek-san extract may produce to improves skin lipid barrier damage. Methods Four-weeks-old NC/Nga mice were divided into four groups: control group (Ctrl, n=10), lipid barrier eliminated group (LBE, n=10), Dexamethasone treatment after lipid barrier elimination group (DXT, n=10), and Sabaek-san extract treatment group after lipid barrier elimination (SBT, n=10). Sabaek-san extract was administered for 3 d after removal of the skin fat barrier in SBT group. Then, we identified changes in external symptoms of the skin, factors affecting skin barrier such as potential of hydrogen (pH), filaggrin, transepidermal water loss (TEWL) and Th2 differentiation factors like Interleukin (IL)-4, Kallikrein Related Peptidase 7 (KLK7), and protease activated receptor 2 (PAR-2) through our immunohistochemistry. Results After lipid barrier elimination, the reduction of morphological skin inflammations was less in SBT group than in LBE and DXT group. Also, pH and TEWL were significantly decreased with SBT group. However, filaggrin was significantly increased in SBT group compared to LBE, DXT, and Ctrl group. All kinds of Th2 differentiation factors (IL-4, KLK7 and PAR-2) were also decreased in SBT compared to the LBE and DXT. Conclusions As a result of this study, SBT administration decreased pH, TEWL, and increased filaggrin, thus participating in recovering damaged skin barrier. Since Th2 differentiation factors were decreased as well, SBT's regulatory effect in sequential immune reactions may be a possible explanation of how it enhances recovery of the damaged lipid barrier.

• Journal of Nutrition and Health
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• v.28 no.10
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• pp.1004-1014
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• 1995

Effect of age and dietary fatty acid composition on immune responses were investigated in Sprague-Dawley male rets. The animals weighing 88.6$\pm$2.2g were fed 10% dietary fat (W/W, 20% of calorie) with P/S ratio of 0.5, 1 and 2, and in each group, there were three different levels of n-6/n-3 fatty acid ratio; 2, 4 and 8(3$\times$3). The experimental periods were 1 month, 6 months and 12 months. The results of this study were; 1) Weights of thymus and spleen were significantly reduced with increasing age, moreover thymus weights were reduced with increasing the degree of unsaturation in dietarty fatty acid at 12 month. 2) The proportion of splenic lymphocyte in the total T-cell was increased with increased with age. The proportion of helper T-cell was not changed, while the proportion of suppressor T-cell was decreased. Thus at 12 month, the ratio of helpe $r^pressor T-cell was appeared to increase significantly, and showed the tendency to increase by consuming the low amount of dieraty n-3 fatty acid. 3) Proliferation stimulated by Con A or PWM reduced significantly at 12 month in which are high in dietary P/S ratio, representing the similar pattern with decrease in thymus weight. 4) Natural killer cell activities were shown significantly higher at 1 month than those at 6 month or 12 month.th.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.175-184
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• 1999

Background: Bronchial asthma is characterized by chronic eosinophilic inflammatory airway disease associated with bronchial hyperresponsiveness and reversible airway obstruction. Bronchial inflammation in asthma may depend in part on the activation of T helper lymphocytes that elaborate proinflammatory cytokines. T helper (Th) lymphocytes can be divided into two categories; Th1 lymphocytes, which secrete IL-2, IL-12 and IFN-$\gamma$, and Th2 lymphocytes, which secrete IL-4, IL-5, IL-6 and IL-10. Th2 lymphocytes appear to induce allergic responses, whereas Th1 lymphocytes induce delayed-type hypersensitivity response. Some infections, such as tuberculosis, cultivate a Th1 immunological environment and inhibit Th2 lymphocytes function. The presence of such infections might inhibit Th2 immune responses and thus protect development of atopic diseases. Method: 15 patients with allergic bronchial asthma, 10 patients with intrinsic bronchial asthma, and 10 healthy volunteers were studied. The serum concentrations of IFN-$\gamma$, IL-12, IL-4, IL-5, and IL-10 were measured by ELISA method and tuberculin skin test was estimated in different groups. Results: The positive response rates of tuberculin test were 46.7% in patients with allergic asthma, 100% in patients with intrinsic asthma and 60% in normal controls. The positive response rates were significantly lower in patients with allergic asthma than those of in patients with intrinsic asthma (p<0.05). Degree of responses to tuberculin test were $12.0{\pm}9.6mm$ in patients with allergic asthma, $18.4{\pm}4.5mm$ in patients with intrinsic asthma and $10.9{\pm}8.8mm$ in normal controls. The degree of responses were significantly reduced in patients with allergic asthma than those of patients with intrinsic asthma (p<0.05). The serum levels of IL-5 in patients with allergic asthma were significantly higher than in patients with intrinsic asthma and normal controls (p<0.05), although it was insignificant. the serum levels of IL-4 and IL-10 in patients with allergic asthma were higher than that of intrinsic asthma and normal controls. The serum levels of IL-12 and IFN-$\gamma$ in patients with allergic asthma and intrinsic asthma were significantly lower than those in normal controls(p<0.05). The serum levels of total immunoglobulin E (IgE) and peripheral blood eosinophile counts in patients with allergic asthma were significantly higher than those in normal controls. Peripheral blood esinophil counts had a significant correlation with the serum levels of total IgE, IL-5 and IL-10 in patients with allergic asthma (p<0.05). Conclusion: These results have showed that Th1 lymphocyte functions were lowered and Th2 lymphocyte functions were elevated in patients with allergic asthma than those in normal controls. Suppression of Th1 lymphocyte functions by activation of Th2 lymphocyte might be one of the important aspects of pathogenesis in allergic bronchial asthma.

• Molecules and Cells
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• v.45 no.11
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• pp.833-845
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• 2022

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as Gata3 and Tcf7. Finally, regarding lung macrophages, hUC-MSCs reduced the total number of macrophages, particularly the proportion of the enhanced monocyte-derived macrophage population. In a closer examination of monocyte-derived macrophages, hUC-MSCs reduced the M2a and M2c populations. In conclusion, hUC-MSCs can be considered as a potential anti-asthmatic treatment given their therapeutic effect on the asthmatic airway inflammation in a murine asthma model by modulating innate immune cells, such as ILC2s, M2a, and M2c macrophages, as well as affecting Tregs and effector T cells.

• Clinical and Experimental Pediatrics
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• v.53 no.11
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• pp.921-930
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• 2010

Juvenile rheumatoid arthritis (JRA) is the most common rheumatic childhood disease; its onset is before 16 years of age and it persists for at least 6 weeks. JRA encompasses a heterogeneous group of diseases that is classified according to 3 major presentations: oligoarthritis, polyarthritis, and systemic onset diseases. These presentations may originate from the same or different causes that involve interaction with specific immunogenetic predispositions, and result in heterogeneous clinical manifestations. An arthritic joint exhibits cardinal signs of joint inflammation, such as swelling, pain, heat, and loss of function; any joint can be arthritic, but large joints are more frequently affected. Extra-articular manifestations include high fever, skin rash, serositis, and uveitis. The first 2 types of JRA are regarded as T helper 1 (Th1) cell-mediated inflammatory disorders, mainly based on the abundance of activated Th1 cells in the inflamed synovium and the pathogenetic role of proinflammatory cytokines that are mainly produced by Th1 cell-stimulated monocytes. In contrast, the pathogenesis of systemic onset disease differs from that of other types of JRA in several respects, including the lack of association with human leukocyte antigen type and the absence of autoantibodies or autoreactive T cells. Although the precise mechanism that leads to JRA remains unclear, proinflammatory cytokines are thought to be responsible for at least part of the clinical symptoms in all JRA types. The effectiveness of biologic therapy in blocking the action of these cytokines in JRA patients provides strong evidence that they play a fundamental role in JRA inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.801-809
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• 2002

CSBHT is known to improve immunological response in mice and humans. In this study, CSBHT effect was examined in the context of CD4+ T cells' survival and TCR/CD3 induced activation responses. Spleen cells from 8 week BALB/c mice were cultured in CSBHT containing medium without activation for 24, 48 hr. The MTS assay and revealed that CSBHT did not stimulate spleen lymphocytes as mitogen. Spleen lymphocytes were treated with anti-CD3e/anti-CD28 antibodies for 48hr. Flow cytometry revealed that activity of T cell decreased with CSBHT concentration. CD4+ T cells were isolated and cultured ,in CSBHT containing medium for 48 hr. CSBHT did not affect survival of sorted CD4+ T cells without any involvement of APC. In order to evaluate the direct effect of CSBHT on helper T cells's proliferative capacity prior to activation, CD4+ T cells are isolated after 24hr of culture in CSBHT containing medium and activated with and without anti-CD3e/anti-CD28 activation for 48hr. A higher level of CD69 was observed in 1 ㎍/㎖ of CSBHT treatment than control using flow cytometry. But low CD69 expression was observed in 5㎍/㎖ of CSBHT treatment. Expression of mRNA for cytokines in CD4+ T cell revealed that IL-2 expression was increased in 1 ㎍/㎖. The expression of IL-2R α, INF- γ were increased with concentration. On the other hand mRNA of IL-4 was decreased in dose dependent manner. Results suggest that CSBHT may be desirable for CD4+ T cell's activity in immune responses. Further more, CSBHT may relatively activate Th1 and inactivate Th2.

• Journal of Microbiology and Biotechnology
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• v.26 no.3
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• pp.469-476
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• 2016

This study was undertaken to evaluate the immunomodulatory effect of dead nano-sized Lactobacillus plantarum (nLp) in RAW 264.7 cells and murine primary splenocytes. nLp is a dead, shrunken, processed form of L. plantarum nF1 isolated from kimchi (a traditional Korean fermented cabbage) and is less than 1 μm in size. It was found that nLp treatment stimulated nitric oxide (NO) production more in RAW 264.7 macrophages than pure live L. plantarum (pLp), and that the stimulatory properties were probably largely derived from its cell wall. In addition, nLp induced murine splenocyte proliferation more so than pLp; in particular, a high dose of nLp (1.0 × 10¹¹ CFU/ml) stimulated proliferation as much as lipopolysaccharide at 2 μg/ml. Moreover, according to our cytokine profile results in splenocytes, nLp treatment promoted Th1 (TNF-α, IL-12 p70) responses rather than Th2 (IL-4, IL-5) responses and also increased Th17 (IL-6, IL-17A) responses. Thus, nLp stimulated NO release in RAW 264.7 cells and induced splenocyte proliferation more so than pLp and stimulated Th1 and Th17 cytokine production. These findings suggested that dead nLp has potential use as a functional food ingredient to improve the immune response, and especially as a means of inducing Th1/Th17 immune responses.