• Biomolecules & Therapeutics
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• 제27권5호
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• pp.466-473
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• 2019

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.

• BMB Reports
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• 제42권12호
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• pp.776-787
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• 2009

T helper (Th) 17 cells have recently been described as a third subset of T helper cells, and have provided new insights into the mechanisms that are important in the development of autoimmune diseases and the immune responses that are essential for effective antimicrobial host defense. Both protective and harmful effects of Th17 responses during infection have been described. In general, Th17 responses are critical for mucosal and epithelial host defense against extracellular bacteria and fungi. However, recent studies have reported that Th17 responses can also contribute to viral persistence and chronic inflammation associated with parasitic infection. It has become evident that the type of microorganisms and the setting in which they trigger the Th17 response determines the outcome of the delicate balancethat exists between Th17 induced protection and immunopathogenesis.

• BMB Reports
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• 제50권1호
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• pp.49-54
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• 2017

Previously, we reported that vitamin C facilitates the CpG demethylation of Foxp3 enhancer in $CD4^+Foxp3^+$ regulatory T cells (Tregs) by enhancing the activity of a DNA demethylase ten-eleven-translocation (Tet). However, it is not clear whether vitamin C affects other helper T cell lineages like T helper type 17 (Th17) cells which are related with Tregs. Here, we show that the expression of interleukin-17A (IL17) increases with the treatment of vitamin C but not with other antioxidants. Interestingly, the upregulation of IL17 was not accompanied by DNA demethylation in Il17 promoter and was independent of Tet enzymes. Rather, vitamin C reduced the trimethylation of histone H3 lysine 9 (H3K9me3) in the regulatory elements of the Il17 locus, and the effects of vitamin C were abrogated by knockdown of jumonji-C domain-containing protein 2 (jmjd2). These results suggest that vitamin C can affect the expression of IL17 by modulating the histone demethylase activity.

• Childhood Kidney Diseases
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• 제22권1호
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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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• 제28권2호
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• pp.211-211
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• 2020

• 한국약용작물학회지
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• 제17권2호
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• pp.90-96
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• 2009

The objective of this study was to investigate the effect of crude ginseng total saponins (CGS) against airway inflammation (AI) and airway hyperresponsiveness (AH) induced by diesel exhaust particles (DEP) in mice. AI and AH were induced by the intratracheal instillation with 0.1 $mg/m{\ell}$ of DEP suspension once a week for 10 weeks combined with ovalbumin (OVA) sensitization. Mice were also treated orally with 75 $mg/m{\ell}$ of CGS, 5 days a week for 10 weeks. Oral CGS treatment decreased in the level of serum immunoglobulin (IgE) and histamine increased by DEP and OVA, and declined respiratory resistance. It also dropped an enhanced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) of mice, and an increased T helper type 2 cell derived cytokine levels such as of interleukin (IL)-4, IL-13 and IL-5 in the BALF. However, it did not influence T helper type 1 cytokine such as interferon-gamma in the BALF. These results indicate that CGS may alleviate allergen-related AI and AH in mice and may play an important role in the modulation of asthmatic inflammation.

• Journal of Ginseng Research
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• 제40권1호
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• pp.18-27
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• 2016

Background: It is not clear whether ginseng affects cyclosporine A (CsA)-induced desirable immunosuppressive action. In this study, we evaluated the immunological influence of combined treatment of ginseng with CsA. Methods: Using CD4+ T cells from mouse spleens stimulated with the T cell receptor (TCR) or allogeneic antigen-presenting cells (APCs), we examined the differentiation of naïve T cells into T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and their cytokine production during treatment by Korean Red Ginseng extract (KRGE) and/or CsA. The influence of KRGE on the allogeneic T cell response was evaluated by mixed lymphocyte reaction (MLR). We also evaluated whether signal transducer and activator of transcription 3 (STAT3) and STAT5 are implicated in this regulation. Results: Under TCR stimulation, KRGE treatment did not affect the population of CD4+interferon gamma ($IFN{\gamma}$)+ and CD4+interleukin (IL)-4+ cells and their cytokine production compared with CsA alone. Under the Th17-polarizing condition, KRGE significantly reduced the number of CD4+IL-17+ cells and CD4+/phosphorylated STAT3 (p-STAT3)+ cells, but increased the number of CD4+CD25+forkhead box P3 (Foxp3)+ cells and CD4+/p-STAT5+ cells compared with CsA alone. In allogeneic APCs-stimulated CD4+ T cells, KRGE significantly decreased total allogeneic T cell proliferation. Consistent with the effects of TCR stimulation, KRGE reduced the number of CD4+IL-17+ cells and increased the number of CD4+CD25+Foxp3+ cells under the Th17-polarizing condition. Conclusion: KRGE has immunological benefits through the reciprocal regulation of Th17 and Treg cells during CsA-induced immunosuppression.

• 한국자원식물학회지
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• 제27권5호
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• pp.567-575
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• 2014

Resveratrol은 천연 stilbene으로 안전성 있는 항염증 활성을 가진 화합물로 알려져 있다. 최근의 연구들에서 resveratrol이 천식, 만성 대장염, 류마티스성 관절염과 같이 염증에 의해 발생하는 다양한 질병을 억제한다고 보고되었다. 이러한 연구들은 resveratrol이 $CD4^+$ helper T cells (Th cells)에 의한 면역반응을 조절할 것이라고 제시하였다. 그러나 resveratrol이 직접적으로 Th cells의 활성화와 분화를 조절하는지 완전히 밝혀지지 않았다. C57BL/6에서 Th cells을 분리하여 다양한 농도의 resveratrol을 세포에 처리하였다. 본 연구에서는 resveratrol이 직접적으로 Th cells의 활성화와 증식을 억제하는 것을 확인하였다. Th cells에 resveratrol을 처리하였을 때 IFN-${\gamma}$, IL-4, IL-17 사이토카인 생성이 농도에 따라 유의하게 감소하였고 또한 Th cells이 이러한 사이토카인들을 분비하는 Th1과 Th2과 Th17으로 분화되는 것이 억제되었다. 그리고 고농도의 resveratrol이 Th cells의 세포사멸을 유도하는 것으로 확인되었다. 본 연구에서는 resveratrol이 Th cells의 활성화와 분화를 직접적으로 억제하는 것을 확인하였으며, 이는 resveratrol이 $CD4^+$ Thcells에 의해 발생되는 자가면역질환의 효과적인 치료법이 될 수 있을 것이라고 제시한다.

• Journal of Microbiology and Biotechnology
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• 제33권6호
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• pp.823-830
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• 2023

Lactococcus lactis is a lactic acid bacterium and used in the dairy food industry. The ameliorating effects of Lactobacillus species on atopic dermatitis (AD) have been extensively studied, but the specific effect of L. lactis strains has not yet been investigated. In this study, the efficacy of L. lactis LB 1022, isolated from natural cheese, was evaluated using RAW 264.7, HMC-1 and HaCaT cell lines and an ovalbumin-sensitized AD mouse model. L. lactis LB 1022 exhibited nitric oxide suppression and anti-allergy and anti-inflammatory activity in vitro. Oral administration of L. lactis LB 1022 to AD mice significantly reduced the levels of IgE, mast cells, and eosinophils, and a range of T cell-mediated T helper Th1, Th2, and Th17-type cytokines under interleukin (IL)-10, transforming growth factor-β (TGF-β), thymus and activation-regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP). In addition, L. lactis LB 1022 treatment increased the concentration of short-chain fatty acids. Overall, L. lactis LB 1022 significantly modulated AD-like symptoms by altering metabolites and the immune response, illustrating its potential as candidate for use in functional food supplements to alleviate AD.

• 생명과학회지
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• 제17권3호통권83호
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• pp.427-434
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• 2007

본 실험에서는 일부 한약재를 이용하여 수지상세포의 활성화에 미치는 영향을 알아보았다. 그 결과, 실험에 사용한 여섯 가지 한약재 중 선별된 천궁과 당귀는 수지상세포의 항원 제시 능력에 영향을 미쳐, T 세포 증식 반응을 증가시켰고, IL-2와 IFN-r의 분비를 증가시키는 것으로 나타났다. 또한 이러한 T 세포의 활성은 수지상세포의 세포표면 단백질인 MHC classII와 CD86, 그리고 CD11c의 발현 증가에 의한 것임을 확인 할 수 있었다. 이상의 실험 결과, 본 실험에서 선별된 천궁과 당귀는 수지상세포를 활성화시키는 효과가 있는 것으로 생각된다.