• Childhood Kidney Diseases
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• v.22 no.1
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• pp.17-21
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• 2018

Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine that is an important trigger and initiator of many allergic diseases. TSLP promotes a T-helper type 2 (Th2) cytokine response that can be pathological. A relationship is formed both at the induction phase of the Th2 response through polarization of dendritic cells to drive Th2 cell differentiation and at the effector phase of the response, by promoting the expansion of activated T cells and their secretion of Th2 cytokines and TSLP. In transgenic mice with TSLP overexpression, it has been reported that TSLP leads to the development of mixed cryoglobulinemic membranoproliferative glomerulonephritis. In addition, TSLP can play an important role in the pathogenesis of IgA nephropathy and systemic lupus erythematosus-related nephritis. From our knowledge of the role of TSLP in the kidney, further studies including the discovery of new therapies need to be considered based on the relationship between TSLP and glomerulonephritis.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.71-76
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• 2015

Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed $PPAR{\gamma}$-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a $PPAR{\gamma}$ ligand, reduced both IL-$1{\beta}$-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-$1{\beta}$. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical $PPAR{\gamma}$ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.

• IMMUNE NETWORK
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• v.9 no.5
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• pp.179-191
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• 2009

Background: The present study examines a hypothesis that short allergen-derived peptides may shift an Aspergillus fumigatus (Afu-) specific TH2 response towards a protective TH1. Five overlapping peptides (P1-P5) derived from Asp f1, a major allergen/antigen of Afu, were evaluated for prophylactic or therapeutic efficacy in BALB/c mice. Methods: To evaluate the prophylactic efficacy, peptides were intranasally administered to naive mice and challenged with Afu-allergens/antigens. For evaluation of therapeutic efficacy, the mice were sensitized with Afu-allergens/antigens followed by intranasal administration of peptides. The groups were compared for the levels of Afu-specific antibodies in sera and splenic cytokines evaluated by ELISA. Eosinophil peroxidase activity was examined in the lung cell suspensions and lung inflammation was assessed by histopathogy. Results: Peptides P1-, P2- and P3 decreased Afu-specific IgE (84.5~98.9%) and IgG antibodies (45.7~71.6%) in comparison with Afu-sensitized mice prophylactically. P1- and P2-treated ABPA mice showed decline in Afu-specific IgE (76.4~88%) and IgG antibodies (15~54%). Increased IgG2a/IgG1 and IFN-${\gamma}$/IL-4 ratios were observed. P1-P3 prophylactically and P1 therapeutically decreased IL-5 levels and eosinophil peroxidase activity. P1 decreased inflammatory cells' infiltration in lung tissue comparable to non-challenged control. Conclusion: Asp f1-derived peptide P1, prophylactically and therapeutically administered to Balb/c mice, is effective in regulating allergic response to allergens/antigens of Afu, and may be explored for immunotherapy of allergic aspergillosis in humans.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.232-239
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• 2010

Stems and roots of Acanthopanax koreanum Nakai were extracted with water and treated on immune cells in order to determine their immunomodulatory activites. Various Th-1 type cytokines were measured using ELISA including interleukin (IL)-2, IL-12, interferon-gamma (IFN-$gamma$), and tumor necrosis factor-alpha (TNF-$\alpha$) secreted by dendritic cells, T-cells, intestinal epithelial cells, natural killer cells, and macrophages. As a result, there was a significant increase in IL-12 and IFN-$\gamma$, secretion, but there was no change in the secretion of TNF-$alpha$. Additionally T-cells slightly increased the secretion of IL-2, but there was a significant increase of IL-2 in intestinal epithelial cells. Therefore, our results suggest that A. koreanum Nakai may act as an immunomodulator by stimulating the cell-mediated immunity which can help the immune system defend against infections or cancer cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.754-761
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• 2008

The purpose of this study was to evaluate the effect of Baekhasuoyijung-Tang(BHSYJT)on mouse T cell cytokines. The proliferation of mouse CD4 T cells under the influence of BHSYJT extract was measured. When mouse CD4 T cell were stimulated with anti-CD3 and anti-CD28 in various concentrations of BHSYJT extract, it increased proliferation of CD4 cells by 28% in $10{\mu}g/m{\ell}$ concentration and by 32% in $100{\mu}g/m{\ell}$ concentration. Treatment of CD4+ T cells stimulated by anti-CD3e and anti-CD28 with BHSYJT resulted in reduction of $IFN-{\gamma}$,but IL-4 levels is not changed. Oral administration of BHSYJT resulted in increase of both CD4+ and CD8+ T cell population in Balb/c mice by 11%. Oral administration of BHSYJT resulted in reduction of serum $IFN-{\gamma}$ level by 27% but, IL-4 level is not changed. CD4+ T cells under Th1/Th2 polarizing conditions for 3 days with BHSYJT resulted in decrease of $IFN-{\gamma}$ level in TH1 cells. Experimental results of this study show that BHSYJT helps to reduce secretion of $IFN-{\gamma}$ by mouse T helper cell in vitro and it had the same effect in vivo. Thus, it can be concluded that use of BHSYJT is an effective treatment for correcting immune imbalance in immune disorders and autoimmune diseases by reducing secretion of cytokine by Th1 cells.

• Archives of Pharmacal Research
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• v.28 no.3
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• pp.343-350
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• 2005

Gamma radiation causes suppression of the immune function, and immune properties are related to cytokine production. In the present study, the polysaccharide, Ginsan, purified from an ethanol-insoluble fraction of Ginseng (Panax ginseng C.A. Meyer, Araliaceae) water extract was studied to assess its effects on the immunosuppressive activities of gamma radiation. Gin­san was found to stimulate murine normal splenocytes by inducing the mRNA expressions of Th1 and Th2 type cytokines, and also restore the mRNA expression of IFN-$/gamma$, Th1 cytokine, after its inhibition by whole-body gamma irradiation. Therefore, Ginsan was found to restore the T lymphocytes function that had been suppressed by gamma irradiation in allogenic MLR (mixed lymphocyte reactions). However, Ginsan exhibited no excessive stimulatory effects on the control group. The above results indicated that Ginsan may constitute a new noble agent for the improvement of gamma radiation-induced immunosuppression.

• BMB Reports
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• v.54 no.3
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• pp.182-187
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• 2021

Leukotriene B4 (LTB4) is a lipid mediator of inflammation that is generated from arachidonic acid via the 5-lipoxygenase pathway. Previous studies have reported that the receptors of LTB4, BLT1, and BLT2 play mediatory roles in the allergic airway inflammation induced by ovalbumin (OVA). However, considering that house dust mites (HDMs) are the most prevalent allergen and well-known risk factor for asthmatic allergies, we are interested in elucidating the contributory roles of BLT1/2 in HDM-induced allergic airway inflammation. Our aim in this study was to investigate whether BLT1/2 play any roles in HDM-induced allergic airway inflammation. In this study, we observed that the levels of ligands for BLT1/2 [LTB4 and 12(S)-HETE (12(S)-hydroxyeicosatetraenoic acid)] were significantly increased in bronchoalveolar lavage fluid (BALF) after HDM challenge. Blockade of BLT1 or BLT2 as well as of 5-lipoxygenase (5-LO) or 12-lipoxygenase (12-LO) markedly suppressed the production of TH2 cytokines (IL-4, IL-5, and IL-13) and alleviated lung inflammation and mucus secretion in an HDM-induced eosinophilic airway-inflammation mouse model. Together, these results indicate that the 5-/12-LO-BLT1/2 cascade plays a role in HDM-induced airway inflammation by mediating the production of TH2 cytokines. Our findings suggest that BLT1/2 may be a potential therapeutic target for patients with HDM-induced allergic asthma.

• The Korea Journal of Herbology
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• v.28 no.1
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• pp.33-42
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• 2013

Objective : Morus alba Linne Root Bark (MRAL) is a medicinal herb in Korean Medicine, known for its anti-inflammatory and anti-allergic properties. However, its mechanisms of action and the cellular targets have not yet been found and the study was developed to investigate the allergic suppressive effect of MRAL. The purpose of this study is to investigate the allergic suppressive effects of MRAL on activation of MC/9 mast cells. Methods : Cytotoxic activity of MRAL (50, 100, 200, 400 ${\mu}g/mL$) on MC/9 mast cells measured using EZ-Cytox cell viability assay kit (WST reagent). The levels of interleukin-5 (IL-5), IL-13 and IL-4, IL-5, IL-6, IL-13 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and real-time PCR respectively. The expression of transcription factors such as GATA-1, GATA-2, NFAT, AP-1 and NF-${\kappa}B$ p65 DNA binding activity were measured by western blot and electrophoresis mobility shift assay (EMSA). Results : Our results indicated that MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) significantly inhibited PMA/Ionomycin-induced production of IL-5 and IL-13 and the expression of IL-4, IL-5, IL-6 and IL-13 mRNA in MC/9 mast cells. Moreover, MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) inhibited PMA/Ionomycin-induced GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos protein expression and NF-${\kappa}B$ p65 DNA binding activity in MC/9 mast cells. Conclusions : In conclusion, we suspect the anti-allergenic activities of MRAL, may be related to the regulation of transcription factors GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 DNA binding assay causing inhibition of Th2 cytokines IL-5 and IL-13 in mast cells.

• Advances in Traditional Medicine
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• v.2 no.1
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• pp.41-46
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• 2002

In our study, the several cytokines were determined in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of Adamantiades-Behcets patients. Adamantiades-Behcets disease (ABD) is a systemic inflammatory disorder and might involve immune dysfunction. High levels of $TNF-\alpha,\;IL-1\beta$ and $IFN-{\gamma}$ indicate the activation of inflammatory reactions and immune system in ABD. Gami-Phedoc-San (GPS) is an Oriental herbal medication, which has been used in Korea for the treatment of ABD. GPS (1 mg/ ml) significantly inhibited the secretion of proinflammatory cytokines, $TNF-\alpha\;and\;IL-1\beta$, compared to absence of GPS (by $50.5{\pm}1.9%$ inhibition for $TNF-\alpha$ and $106.9{\pm}16.8%$ for $IL-1\beta$). GPS also inhibited the production of $IFN-\gamma$, immunoregulatory Th1 cytokine, by $78.4{\pm}2.8%$. The inhibitory effects of GPS on cytokine secretion showed dose-dependent manner, and the pre-treatment of 1 mg/ml GPS had better effects than immunosuppressive drug for treatment of ABD, cyclosporin A. Our results suggest that GPS treatment for ABD patients might have pharmacological activity of immune and inflammatory responses through the cytokine modulation.

• The Korea Journal of Herbology
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• v.34 no.2
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• pp.41-47
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• 2019

Objectives : A traditional herbal prescription, Kyung-Ok-Ko (KOK), has long been used in oriental medicine as an invigorant for age-related diseases, such as amnesia and stroke. However, the beneficial value of KOK for immune responses is largely unknown. Based on the above mentioned effects of KOK, other previous reports, and its use in traditional medicine, we hypothesized that KOK displays beneficial effects against methotrexate (MTX)-induced immune suppression. Methods : We investigated the effects of KOK (0.6 g/kg/day, oral (p.o.)) on deteriorated immunity caused by MTX (2 mg/kg/day, p.o.) in an immune suppression mouse model. MTX was fed to mice once a day for 7 days. After the immune responses of the mice deteriorated by MTX treatment, KOK in water was fed to the mice once a day for 14 days. We then measured the expression levels of various cytokines, such as T helper cell (Th1, Th2) cytokines, and the number of immune cells, such as spleen T cells, B cells, and macrophages. Results : The data showed that MTX decreased Th1 profiles (interferon $(IFN)-{\gamma}$, interleukin (IL)-2, IL-12) and the number of immune cells, and increased Th2 profiles (IL-4, IL-5, IL-13), which were normalized significantly by post-administration of KOK. However, there was no significant difference in body-weight gain between MTX- and KOK-treated mice. Conclusion : These results indicate that KOK has immune-enhancing functions and reduces immunotoxicity of MTX, suggesting that supplementation with KOK will improve immune responses clinically and be useful for the prevention of immune-related diseases.