• The Journal of Pediatrics of Korean Medicine
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• v.35 no.4
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• pp.156-166
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• 2021

Objectives The purpose of this study is to confirm the regulate effect of T helper (Th) 2 differentiation that Baekho-tang extract may produce to improves skin lipid barrier damages. 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 Baekho-tang extract treatment group after lipid barrier elimination group (BHTT, n=10). Baeko-tang extract was administered for 3 days after removal of the skin fat barrier in BHTT group. Then, we identified changes in external symptoms of the skin, factors affecting skin barrier such as potential of hydrogen (pH), filaggrin (FLG), 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 BHTT group than in LBE group and DxT group. Also, pH and TEWL were significantly decreased with BHTT group. However, FLG was significantly increased in BHTT group compared to LBE, DxT, and Ctrl group. All kinds of Th2 differentiation factors (IL-4, KLK7 and PAR-2) were also decreased in BHTT compared to the LBE and DxT. Conclusions As a result of this study, BHT administration decreased pH, TEWL, and increased FLG, thus participating in recovering damaged skin barrier. Since Th2 differentiation factors were decreased as well, BHT's regulatory effect in sequential immune reactions may be a possible explanation of how it enhances recovery of the damaged lipid barrier.

• 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.

• Molecules and Cells
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• v.44 no.5
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• pp.318-327
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• 2021

CD4+ T helper (Th) cells play a crucial role in the modulation of innate and adaptive immune responses through the differentiation of Th precursor cells into several subsets, including Th1, Th2, Th17, and regulatory T (Treg) cells. Effector Th and Treg cells are distinguished by the production of signature cytokines and are important for eliminating intracellular and extracellular pathogens and maintaining immune homeostasis. Stimulation of naive Th cells by T cell receptor and specific cytokines activates master transcription factors and induces lineage specification during the differentiation of Th cells. The master transcription factors directly activate the transcription of signature cytokine genes and also undergo post-translational modifications to fine-tune cytokine production and maintain immune balance through cross-regulation with each other. This review highlights the post-translational modifications of master transcription factors that control the differentiation of effector Th and Treg cells and provides additional insights on the immune regulation mediated by protein argininemodifying enzymes in effector Th cells.

• Journal of Microbiology and Biotechnology
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• v.17 no.12
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• pp.2056-2060
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• 2007

Transcription factor GATA-3 is the critical transcription factor for Th2 cell differentiation. In spite of its importance in Th2 cell differentiation, the molecular mechanism for its action in Th2 differentiation is poorly understood. Previous studies have suggested that GATA-3 may be involved in the chromatin remodeling in the Th2 cytokine locus. To determine whether GATA-3 exerts its effect on its target sites in the extrachromosomal status, cell transfection assay was performed. In this assay, 800 bp IL4 promoter-luciferase constructs linked with GATA-3 target sites were transfected into the M12 B cell line, D10 mouse Th2 cell lines, and human T lymphoma Jurkat cell lines with or without the GATA-3 expression vector. The GATA-3 effects on its target sites were minimal in the extrachromosomal status, supporting the previous propositions that GATA-3 functions at the chromatin level by remodeling chromatin structure.

• Clinical and Experimental Reproductive Medicine
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• v.31 no.1
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• pp.67-74
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• 2004

Objective: This study was to examine in vitro neural cell differentiation pattern of the genetically modified human embryonic stem cells expressing tyrosine hydroxylase (TH). Materials and Methods: Human embryonic stem (hES, MB03) cell was transfected with cDNAs cording for TH. Successful transfection was confirmed by western immunoblotting. Newly transfected cell line (TH#2/MB03) was induced to differentiate by two neurogenic factors retinoic acid (RA) and b-FGF. Exp. I) Upon differentiation using RA, embryoid bodies (EB, for 4 days) derived from TH#2/MB03 cells were exposed to RA ($10^{-6}M$)/AA ($5{\times}10^{-2}mM$) for 4 days, and were allowed to differentiate in N2 medium for 7, 14 or 21 days. Exp. II) When b-FGF was used, neuronal precursor cells were expanded at the presence of b-FGF (10 ng/ml) for 6 days followed by a final differentiation in N2 medium for 7, 14 or 21 days. Neuron differentiation was examined by indirect immunocytochemistry using neuron markers (NF160 & NF200). Results: After 7 days in N2 medium, approximately 80% and 20% of the RA or b-FGF induced Th#2/MB03 cells were immunoreactive to anti-NF160 and anti-NF200 antibodies, respectively. As differentiation continued, NF200 in RA treated cells significantly increased to 73.0% on 14 days compared to that in b-FGF treated cells (53.0%, p<0.05), while the proportion of cells expressing NF160 was similarly decreased between two groups. However, throughout the differentiation, expression of TH was maintained ($\sim$90%). HPLC analyses indicated the increased levels of L-DOPA in RA treated genetically modified hES cells with longer differentiation time. Conclusion: These results suggested that a genetically modified hES cells (TH#2/MB03) could be efficiently differentiated in vitro into mature neurons by RA induction method.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.344-347
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• 2005

Helper T(Th) cells regulate immune response by producing various kinds of cytokines in response to antigen stimulation. The regulatory functions of Th cells are promoted by their differentiation into two distinct subsets, Th1 and Th2 cells. Th1 cells are involved in inducing cellular immune response by activating cytotoxic T cells. Th2 cells trigger B cells to produce antibodies, protective proteins used by the immune system to identify and neutralize foreign substances. Because cellular and humoral immune responses have quite different roles in protecting the host from foreign substances, Th cell differentiation is a crucial event in the immune response. The destiny of a naive Th cell is mainly controlled by cytokines such as IL-4, IL-12, and IFN-${\gamma}$. To understand the mechanism of Th cell differentiation, many mathematical models have been proposed. One of the most difficult problems in mathematical modeling is to find appropriate kinetic parameters needed to complete a model. However, it is relatively easy to get qualitative or linguistic knowledge of a model dynamics. To incorporate such knowledge into a model, we propose a novel approach, fuzzy continuous Petri nets extending traditional continuous Petri net by adding new types of places and transitions called fuzzy places and fuzzy transitions. This extension makes it possible to perform fuzzy inference with fuzzy places and fuzzy transitions acting as kinetic parameters and fuzzy inference systems between input and output places, respectively.

• Journal of Microbiology and Biotechnology
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• v.19 no.2
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• pp.208-214
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• 2009

Steroid hormones have long been known to have a profound influence on the immune system. Although the functions of the nuclear receptors in the development of T cells are fairly well studied, the differential expression of these receptors in T helper cells is poorly understood. Here, we investigated the differential expression of nuclear receptors and coregulators in Th1 and Th2 cells by genome-wide micro array analysis. The result showed that several nuclear receptors and coregulators are differentially expressed in these cells. The result was confirmed by RT-PCR. The result showed that $RXR{\alpha}$ is highly expressed in Th2 cells. Overexpression of $RXR{\alpha}$ in a Jurkat human T cell line induced IL4 but not IFN-${\gamma}$ gene expression, suggesting that $RXR{\alpha}$ plays a selective role in Th1 and Th2 differentiation. In summary, these results suggest that Th1/Th2 differentiation is influenced by differential regulation of nuclear receptors and coregulators.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.75-75
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• 2003

Since the establishment of embryonic stem cell, pluripotency of the cells was known to allow differentiation of the cells into various cell types consisting whole body. Several protocols have been developed to induce expression of specific genes.. However, no precise protocol that will generate a single type of the cells from stem cells has been reported. In order to produce cells suitable for transplantion into brain of PD animal model, which arouse due to a progressive degeneration of dopaminergic neurons in midbrain, human embryonic stem cell (hESC, MB03) was transfected with cDNAs cording for tyrosine hydroxylase (TH). Successful transfection was confirmed by western immunoblotting. Newly transfected cell line (TH#2/MB03) was induced to differentiate by the two neurogenic factors retinoic acid (RA) and b-FGF. Exp. I) Upon differentiation using RA/ascorbic acid (AA), embryoid bodies (EB, for 4days) derived from hES cells were exposed to RA (10$^{-6}$ M)/AA (50 mM) for 4 days, and were allowed to differentiate in N2 medium for 7, 14, 21, or 28 days. Exp. II) When bFGF was used, neuronal precursor cells were selected for 8 days in N2 medium after EB formation. After selection, cells were expanded at the presence of bFGF (20 ng/ml) for another 6 days followed by a final differentiation in N2 medium for 7, 14, 21 or 28 days. By indirect immunocytochemical studies, proportion of cells expressing NF200 increased rapidly from 20% at 7 days to 70 % at 28 days in RA/AA-treated group, while those cells expressing NF160 decreased from 80% at 7 days to 10% at 28 days upon differentiation in N2 medium. However, in differentiation by RA/AA treatment system, there was a significant increase in proportion of neuron maturity (73%) at day 14 after N2 medium. TH#2/MB03 cells expressing TH are >90% when matured at the absence of either bDNF or TGF-$\alpha$. These results suggested that TH#2/MB03 cells could be differentiated in vitro into mature neurons by RA/AA.

• Korean Journal of Plant Resources
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• v.27 no.5
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• pp.567-575
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• 2014

Resveratrol is a naturally occurring stilbene which is safe and well-described compound with a potent anti-inflammatory activity. Recent studies suggested that resveratrol suppressed various inflammation mediated diseases such as asthma, chronic colitis, rheumatoid arthritis, and type 1 diabetes. These studies indicated that resveratrol might directly modulate $CD4^+$ helper T cells (Th cells)-mediated immune responses. However, it is not fully elucidated whether resveratrol directly regulates $CD4^+$ Th cell activation and differentiation. In the present study, $CD4^+$ Th cells were purified from C57BL/6 and treated with various concentrations of resveratrol. We found that resveratrol directly suppressed $CD4^+$ Th cells activation, leading to a defect in T cell proliferation. When $CD4^+$ Th cells were treated with resveratrol, cytokine production was also significantly reduced in a dose dependent manner. In accordance with these results, resveratrol even inhibited $CD4^+$ Th cells differentiation into Th1, Th2 or Th17, which produces IFN-${\gamma}$, IL-4 or IL-17 respectively. We also found that resveratrol could induce apoptosis of $CD4^+$ T cells at a high concentration. Our data demonstrated that resveratrol inhibited directly $CD4^+$ Th cells activation and differentiation. It suggests that resveratrol could be an efficient therapeutic strategy for autoimmune diseases in which $CD4^+$ Th cells play a critical role.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.3
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• pp.63-70
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• 2007

Objectives : Atopic dermatitis is a recurrent or chronic eczematous skin disease with severe pruritus. Although the pathogenic mechanisms of atopic dermatitis are yet unknown, recently hyperresponsive Th2 cells in the acute phase are reported as the important mechanisms. Cheonggisan(CGS) is used in oriental clinics for curing acute skin lesions of eczema, atopic dermatitis or urticaria. There have been no studies on the therapeutic mechanism of CGS for curing atopic dermatitis. We aimed to find out the therapeutic mechanism of CGS on atopic dermatitis, so we observed Th2 cell differentiation in EL 4 cells and $NF-kB$ p65 activation in RAW 264.7 cells. Materials and Methods : EL 4 cells were induced the increase of IL-4 mRNA expression by phorbol-12-myristate-13-acetate(PMA) and 4-tert-Octylphenol(OP) and treated with CGS extract. RAW 264.7 cells were induced the increase of cyclooxygenase(COX)-2 mRNA expression by lipopolysaccharide(LPS) and treated with CGS extract. Results : The PMA and OP induced IL-4 mRNA expression was dose-dependantly decreased in CGS treated EL 4 cells. The LPS-induced COX-2 mRNA expression was dose-dependantly decreased in CGS treated RAW 264.7 cells. Conclusion : The results may suggest that the CGS inhibits Th2 cell differentiation in EL 4 cells and inhibits $NF-kB$ p65 activation in RAW 264.7 cells.