• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1027-1031
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• 2005

In the present study, wogonin, a major flavone isolated from Scutellaria Radix were examined for its imunosuppressive activity on the 2,4-dinitro-fluorobenzene (DNFB)-induced delayed type hypersensitivity (DTH) in C3H/HeN mice. This compound inhibited selectively $TNF-\alpha$ and IL-4, but not IL-6, IL-10 and $IFN-\gamma$ on DNFB-induced Th1 and Th2 cytokines in a concentration-dependent manner. Interestingly, this compound increased the expression of heme oxygenase-1 (HO-1) in a concentration-dependent manner The above results reveal that wogonin possesses anti-inflammatory, humoral and cellular immunomodulatory, and stress reducing activities on the DNFB-induced DTH in mice and these properties may contribute to the anti-atopic dermatitis activity of Scutellaria Radix.

• YAKHAK HOEJI
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• v.56 no.6
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• pp.366-371
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• 2012

In this present study, we determined whether or not there is an immunoadjuvant effect of ochnaflavone, a biflavone isolated from Lonicera japonica. As an antigenic source, the cell wall (CACW) of Candida albicans, a fungal pathogen, was used. CACW consists of 95% carbohydrate (mannan). In the experiments, BALB/c mice were immunized with emersion forms of CACW combined with or without ochnaflavone (Och) in the presence of IFA containing mineral oil or CACW alone. Then, the amounts of antisera collected from these mice groups were measured by the ELISA method. Data from these experiments showed that CACW combined with Och (CACW/Och/IFA) provoked the production of antisera app. 2.2 or 5 times more than the corresponding CACW/IFA or CACW alone (CACW/DPBS), respectively, in mice (P<0.05). We further examined the immune response type induced by Och. Analysis of the values of the IgG1/IgG2a ratios obtained from IgG isotyping revealed that Och induced Th2-immunity more dominantly than Th1. This finding was confirmed by cytokine profile. CACW/Och/IFA formulation induced IL-4 (Th2-type cytokine) more than IFN${\gamma}$ (Th1-type cytokine) as compared with CACW/IFA and CACW/DPBS formulations (P<0.05). All data combined, Och appears to have an immunoadjuvant activity that may convert Th1 immunity into Th2 immunity.

• Animal cells and systems
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• v.10 no.1
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• pp.15-20
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• 2006

Allergic inflammation is thought to be a Th2 cell-dominant immune response during which tissue-resident fibroblasts produce chemokines which contribute to the recruitment of migratory leukocytes to sites of tissue injury. Thymus and activation-regulated chemokine (TARC; CCL17) is a potent member of the CC chemokine family and a selective chemoattractant for Th2 cells. In order to study the regulatory profiles of TARC production by $TNF-{\alpha}$, $IFN-{\gamma}$, and Il-4 in human normal skin fibroblast, CCD-986sk cell line was used. The expression of TARC protein was measured using ELISA, and mRNA level was detected by RT-PCR. The combination of $TNF-{\alpha}$ and IL-4 induced a time-and dose-dependent synergistic increase in the expression of TARC at both protein and mRNA levels in the cultured human skin fibroblasts. Exposure of the cells to single cytokine had no effect on TARC expression. The high concentration (100 ng/ml) and long incubation time (72 h) of $IFN-{\gamma}$ further enhanced the TARC production induced by $TNF-{\alpha}$/lL-4 in the skin fibroblast. This synergistic effect of Th1 and Th2 type cytokines on TARC production by skin fibroblasts may contribute to the inflammatory cell infiltration and tissue damage with allergic inflammation.

• BMB Reports
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• v.51 no.5
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• pp.207-208
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• 2018

Chitinase-Like Proteins (CLPs) are an evolutionarily conserved protein which lose their enzymatic activity for degrading chitin macromolecules. Chitinase-3-like-1 (Chi3l1) is a type of CLP that is highly expressed in epithelial cells, macrophages, etc., and is known to have correlations with type 2 inflammation and cancer. Although the increased level of Chi3l1 in the blood was reported in various disease patients, the function of Chi3l1 in adaptive immunity has been totally unknown. Recently, we found that Chi3l1 is expressed in T cells and has a negative regulatory role in T-cell activation and proliferation. A genetic ablation study of Chi3l1 in T cells showed hyperresponsiveness to TcR stimulation, which increased proliferation and Th1 differentiation. A significant increase of $IFN{\gamma}$ signaling in Chi3l1-deficient T cells synergistically increased Th1 and CTL functions against melanoma cells in vitro and in vivo. In addition, targeted knockdown by Chi3l1 siRNA complexed with the cell-penetrating peptide dNP2, which showed decreased pulmonary melanoma metastasis with increased infiltration of Th1 and CTL in the lung. This study first suggests that Chi3l1 is a novel regulator of Th1/CTL responses and could be a target for treating cancer to increase tumor immunity.

• Journal of Microbiology and Biotechnology
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• v.23 no.5
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• pp.724-730
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• 2013

We investigated the effects of orally administered probiotic bacteria (Lactobacillus species) as allergic immune modulators in ovalbumin (OVA)-sensitized mice. BALB/c mice were intraperitoneally injected with OVA twice at a 2-week interval for allergy sensitization. The mice were then orally administered Lactobacillus casei YIT9029 (L1), L. casei HY7201 (L2), L. brevis HY7401 (L3), or L. plantarum HY20301 (L4) every 2 days for 3 weeks. Total IgE levels significantly decreased in sera of L3-administered mice but increased in the other groups. OVA-specific IgE levels decreased slightly in sera of mice administered L1, L3, and L4 but increased significantly in L2-administered mice. In passive cutaneous anaphylaxis (PCA) using sera from administered mice, only the L3-administered group showed reaction inhibition. High expression of TLR-2 with interferon (IFN)-${\gamma}$ stimulation on peripheral blood mononuclear cells occurred in L3- or L4-administered mice. Th1 cytokines, including IFN-${\gamma}$ and interleukin (IL)-12, increased in splenocytes of L3-administered mice; however, IL-4 decreased in L1- and L4-administered groups; IL-5 decreased in all experimental groups. IL-6 decreased in the L3-administered group; and IL-10 decreased in L1-, L2-, and L3-administered groups. L3 induced antiallergic effects by increasing Th1 cytokines, decreasing Th2 cytokines, and inhibiting the PCA reaction, whereas L2 administration increased allergic effects.

• IMMUNE NETWORK
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• v.12 no.5
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• pp.196-206
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• 2012

Besides their role as building blocks of protein, there are growing evidences that some amino acids have roles in regulating key metabolic pathways that are necessary for maintenance, growth, reproduction, and immunity. Here, we evaluated the modulatory functions of several amino acids in protective immunity against mucosal infection of herpes simplex virus type 1 (HSV-1). We found that glutamine (Gln) and leucine (Leu) showed enhanced protective immunity to HSV-1 mucosal infection when two administration of Gln and single administration of Leu per day, but not when administered in combinations. Ameliorated clinical signs of HSV-1 challenged mice by the intraperitoneal administration of Gln and Leu were closely associated with viral burden and IFN-${\gamma}$ production in the vaginal tract at 2 and 4 days post-infection. In addition, the enhanced production of vaginal IFN-${\gamma}$ appeared to be caused by NK and HSV-1 antigen-specific Th1-type CD4+ T cells recruited into vaginal tract of mice treated with Gln and Leu, which indicates that IFN-${\gamma}$, produced by NK and Th1-type CD4+ T cells, may be critical to control the outcome of diseases caused by HSV-1 mucosal infection. Collectively, our results indicate that intraperitoneal administration of Gln and Leu following HSV-1 mucosal infection could provide beneficial effects for the modulation of protective immunity, but dosage and frequency of administration should be carefully considered, because higher frequency and overdose of Gln and Leu, or their combined treatment, showed detrimental effects to protective immunity.

• Korean Journal of Food Science and Technology
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• v.38 no.6
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• pp.829-834
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• 2006

LP-BM5 murine leukemia retrovirus induces the immune dysfunction by imbalanced secretion of Th1 and Th2 cytokines in the murine AIDS model. In the present study, it was investigated whether pycnogenol (Pyc) administration could deactivate $NF-{\kappa}B$ to regulate the gene expression of Th1 and Th2 cytokines in C57BL/6 mice with murine AIDS. Treatment with Pyc for 12 weeks significantly inhibited the loss of body weight and enlargement of spleen and lymph node usually seen with AIDS. Moreover, Pyc increased the plasma level of Th1 cytokines, IL-2 and $IFN-{\gamma}$, while reducing the plasma level of Th2 cytokines, IL-6, IL-10, and $TNF-{\alpha}$. In primary culture of splenocytes, mRNA expression of Th2 cytokines was suppressed, but that of Th1 cytokines was not affected. The LP-BM5 retrovirus infection stimulated the cytoplasmic activation of $NF-{\kappa}B$ and nuclear translocation of $I-{\kappa}B$, whereas Pyc administration significantly reduced $NF-{\kappa}B$ activation and $I-{\kappa}B$ degradation. These results suggested that the inhibitory effect of Pyc on Th2 cytokines in mice with murine AIDS was dependent on suppression of the $NF-{\kappa}B$ signaling pathway and was not dependent on $INF-{\gamma}$ level, which regulates Th2 cytokines.

• Korean Journal of Medicinal Crop Science
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• v.26 no.1
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• pp.72-81
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• 2018

Background: Polysaccharides are the most important functional constituent in Astragalus membranaceus. The purpose of the present study was to evaluate the effect of polysaccharides isolated from the aboveground parts of A. membranaceus (AMA) and polysaccharides isolated from the roots of A. membranaceus (AMR) immune function by modulated cytotoxic T cell and Th1- and Th2-related cytokines kinetics. Methods and Results: Sprague-Dawley rats were randomly divided into exhaustive exercise case groups and non-exercise case, AMA and AMR samples were administered orally for 30 days (500 mg/kg/day and 10 mg/kg/day, respectively) and were compared to those rats in the groups fed commercial sports drink (SPD) and vehicle. Both exhaustive exercise groups and non-exercise groups had a lower ratio of $CD4^+$ and $CD8^+$ cells in the spleens of the rat fed AMA and AMR compared to those in the rats fed SPD and vehicle group. These results suggested that AMA and AMR promote an increase in the proportion of cytotoxic T cells. The IL-4-producing T lymphocytes decreased significantly in the AMR (10 mg/kg/day) group compared to SPD and vehicle, whereas the AMA group increased the IL-4 concentration more than the SPD and vehicle in exhaustive exercise group. However, the populations of IFN-${\gamma}$-producing T lymphocytes of AMR and AMA increased. AMA decreased the concentration of IFN-${\gamma}$ to inhibit the Th1 response and thereby increased the concentration of IL-4 to induce a Th2 response that was related to humoral immunity in the non-exercise group. Conclusions: These results showed that, in addition to Th1/Th2 regulation, AMR and AMA played an important immuno-modulatory role after exhaustive exercise-induced Th1/Th2 lymphocyte imbalance, which might be correlated with cytokine producing immunoregulatory cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.10
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• pp.1329-1335
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• 2006

LP-BM5 murine leukemia retrovirus induces the excessive oxidative stress and immune dysfunction leading to B cell leukemia and murine AIDS with cytokine dysfunction. In the present study, the immune restoratory effect of antioxidant hormone dedydroepiandrosterone sulfate (DHEAS) was investigated in the primary splenocytes from LP-BM5 retrovirus-infected C57BL/6 mice. DHEAS significantly increased T and B cell response to mitogen and normalized the unbalanced production of Th1/Th2 type cytokines. In particular, both protein and mRNA expression of IL-4, IL-6, and $TNF-\alpha$ were down-regulated by DHEAS treatment whereas IL-2 and $IFN-\gamma$ level were increased. This result suggests that DHEAS directly or indirectly regulates the gene expression of Th1/Th2 type cytokines in transcription level. In addition, DHEAS treatment decreased the hepatic lipid peroxidation and preserved vitamin E level in liver cells. These results suggested that DHEAS could effectively prevent immune dysfunction by regulating cytokine secretion and preventing the oxidative stress in murine AIDS.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.760-764
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• 2007

We investigated that the immunomodulating activity of BL18 (Ganshu) acupuncture on the experimental liver metastasis model of mice. NA (non-acupoint)- and BL18-treatment enhanced the mitogenic activity of BALB/c whole splenocytes induced by various mitogenic stimuli. Acupuncture treatment tended to increase splenocytes differentiation even though did not show significance. Acupuncture treatment caused a marked increase of production of Th1 cytokine (IFN-${\gamma}$) and Th2 cytokine (IL-4) by splenocytes and IL-12 and IFN-Y by macrophages. The increase of cytokine production on BL18-treated group was more pronounced compared to NA-treated group. The liver weight of NA- and BL18-treated group decreased compared to tumor group, but did not showed significant differences.