• Title/Summary/Keyword: regulatory T cells

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Crude Extract and Solvent-Partitioned Fractions of the Halophyte Atriplex gmelinii Inhibit Adipogenesis in 3T3-L1 Preadipocytes (3T3-L1 지방전구세포에서 염생식물 Atriplex gmelinii의 조추출물과 용매 분획물의 지방세포분화 억제)

  • Jung Im Lee;Jung Hwan Oh;Chang-Suk Kong;Youngwan Seo
    • Journal of Korean Medicine for Obesity Research
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    • v.23 no.2
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    • pp.69-77
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    • 2023
  • Objectives: Atriplex gmelinii C. A. Meyer is a halophyte belonging to the Chenopodiaceae family, and its young leaves and stems are used as fodder for livestock. The aim of the present study was to investigate the effects of A. gmelinii extract and its solvent fractions on lipid accumulation during adipogenesis of 3T3-L1 preadipocytes. Methods: The samples of A. gmelinii were separately extracted using methylene chloride and methanol. Subsequently, they were combined to formulate the initial extract, which was then partitioned based on polarity to prepare solvent fractions. Oil Red O staining was employed to measure lipid accumulation during the differentiation of 3T3-L1 preadipocytes. To verify cytotoxicity in 3T3-L1 cells, MTT assays were conducted. The expression levels of transcription factors in 3T3-L1 preadipocytes were measured through Western blotting analysis. Results: At 50 ㎍/mL, treatment of A. gmelinii extract and its solvent fractions during the differentiation of 3T3-L1 preadipocytes significantly diminished lipid accumulation with no noteworthy cytotoxicity on cell viability. Additionally, when investigating the biochemical pathways that underlie the prevention of lipid accumulation using solvent fractions, it was found that the n-BuOH and n-hexane fractions significantly decreased the expression of key transcription factors involved in the generation of fat, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP1c). Conclusions: These findings indicate that A. gmelinii can effectively reduce the accumulation of fat in 3T3-L1 adipocytes, making it a potentially valuable material for mitigating and preventing obesity.

MicroRNA Regulation in Systemic Lupus Erythematosus Pathogenesis

  • Yan, Sheng;Yim, Lok Yan;Lu, Liwei;Lau, Chak Sing;Chan, Vera Sau-Fong
    • IMMUNE NETWORK
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    • v.14 no.3
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    • pp.138-148
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    • 2014
  • MicroRNAs (miRNAs) are endogenous small RNA molecules best known for their function in post-transcriptional gene regulation. Immunologically, miRNA regulates the differentiation and function of immune cells and its malfunction contributes to the development of various autoimmune diseases including systemic lupus erythematosus (SLE). Over the last decade, accumulating researches provide evidence for the connection between dysregulated miRNA network and autoimmunity. Interruption of miRNA biogenesis machinery contributes to the abnormal T and B cell development and particularly a reduced suppressive function of regulatory T cells, leading to systemic autoimmune diseases. Additionally, multiple factors under autoimmune conditions interfere with miRNA generation via key miRNA processing enzymes, thus further skewing the miRNA expression profile. Indeed, several independent miRNA profiling studies reported significant differences between SLE patients and healthy controls. Despite the lack of a consistent expression pattern on individual dysregulated miRNAs in SLE among these studies, the aberrant expression of distinct groups of miRNAs causes overlapping functional outcomes including perturbed type I interferon signalling cascade, DNA hypomethylation and hyperactivation of T and B cells. The impact of specific miRNA-mediated regulation on function of major immune cells in lupus is also discussed. Although research on the clinical application of miRNAs is still immature, through an integrated approach with advances in next generation sequencing, novel tools in bioinformatics database analysis and new in vitro and in vivo models for functional evaluation, the diagnostic and therapeutic potentials of miRNAs may bring to fruition in the future.

Effects of Lonicera caerulea extract on adipocyte differentiation and adipogenesis in 3T3-L1 cells and mouse adipose-derived stem cells (MADSCs) (댕댕이나무 열매 추출물이 지방전구세포와 마우스 지방유래줄기세포의 분화 및 지방 생성 억제에 미치는 영향)

  • Park, Miey;Lee, Changho;Lee, Hae-Jeung
    • Journal of Nutrition and Health
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    • v.52 no.1
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    • pp.17-25
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    • 2019
  • Purpose: Obesity is a major health problem of global significance because it is clearly associated with an increased risk of health problems, such as nonalcoholic fatty liver disease (NAFLD), diabetes, cardiovascular diseases, and cancer. Lonicera caerulea (LC) originates from high mountains or wet areas and has been used as a traditional medicine in northern Russia, China, and Japan. LC contains a range of bioactive constituents, such as vitamins, minerals, and polyphenols. This study examined the anti-obesity effects of LC during differentiation in preadipocytes. Methods: The cell viability assay was performed after the differentiation of 3T3-L1 cells for 7 days. Oil Red O staining was used to visualize the changes in lipid droplets in 3T3-L1 cells and mouse adipose-derived stem cells (MADSCs). The mRNA expression of obesity-related genes was determined by quantitative real-time PCR. Results: According to the results of Oil Red O staining, the lipid levels and size of lipid droplets in the adipocytes were reduced and the LC extract (LCE, 0.25-1 mg/mL) markedly inhibited adipogenesis in a dose-dependent manner. The treatment of LCE also decreased the mRNA expression of peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), CCAAT/enhancer binding protein-${\alpha}$ ($C/EBP{\alpha}$), and sterol regulatory element binding protein 1 (SREBP1) in 3T3-L1 cells. Western blot analysis showed that the $PPAR{\gamma}$, $C/EBP{\alpha}$, and SREBP1 protein levels in both 3T3-L1 and MADSC were reduced in a dose-dependent manner. Conclusion: These results suggest that LCE can inhibit adipogenic differentiation through the regulation of adipogenesis-related markers.

Control of Allergy with Probiotics and Its Safety (프로바이오틱스에 의한 알레르기 질환 제어 및 안전성)

  • Lee, Yewon;Yoon, Yohan
    • Journal of Dairy Science and Biotechnology
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    • v.38 no.1
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    • pp.19-26
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    • 2020
  • Allergic diseases, including atopic dermatitis, asthma, allergic rhinitis, and food allergies, could be caused by dysbiosis that results in an immune system imbalance. The incidence of allergic diseases has been increasing and they are now one of the most common diseases throughout the world. Recently, probiotics have been suggested as an alternative intervention for the prevention and treatment of allergic diseases. Probiotics are endogenous microflora with functional effects within hosts. They have various clinical and immunological capacities and have recently been considered as a supplement for the treatment and prevention of allergic diseases. Probiotic bacteria modulate immune cells such as Th1, Th2, and regulatory T cells that are correlated with protection against atopic dermatitis, however, safety concerns for the use of probiotics have been raised. Therefore, further research is needed to clarify the efficacy and safety of probiotics in the treatment of allergic diseases.

Tyndallized Lactobacillus plantarum HY7712 Restores Whole-Body γ-Irradiation-Impaired Th Cell Differentiation in Mice

  • Jang, Se-Eun;Ko, Da-Bin;Ahn, Young-Tae;Sim, Jae-Hun;Kim, Cha Soon;Kim, Dong-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.27 no.12
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    • pp.2237-2240
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    • 2017
  • In the present study, we investigated the effect of tyndallized HY7712 (tHY7712) on the expression of Th cell specific transcription factors and cytokines in whole-body ${\gamma}$-irradiated mice. Oral administration of tHY7712 strongly recovered the ${\gamma}$-irradiation-suppressed expression of helper T (Th) cell- and regulatory T cell-related transcription factors and cytokines, such as T-bet, Foxp3, IFN-${\gamma}$, TNF-${\alpha}$, and IL-10, and suppressed Th2 cell-associated transcription factor and cytokine GATA3 and IL-5, respectively. Furthermore, compared with the control, tHY7712 treatment also restored ${\gamma}$-irradiation-impaired natural killer and cytotoxic T cell activities against YAC-1 tumor cells to 97.8% and 98.6%, respectively.

Pathogenesis of minimal change nephrotic syndrome: an immunological concept

  • Kim, Seong Heon;Park, Se Jin;Han, Kyoung Hee;Kronbichler, Andreas;Saleem, Moin A.;Oh, Jun;Lim, Beom Jin;Shin, Jae Il
    • Clinical and Experimental Pediatrics
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    • v.59 no.5
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    • pp.205-211
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    • 2016
  • Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia. Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children. The pathogenesis of MCNS still remains unclear, however, several hypotheses have been recently proposed. For several decades, MCNS has been considered a T-cell disorder, which causes the impairment of the glomerular filtration barrier with the release of different circulating factors. Increased levels of several cytokines are also suggested. Recently, a "two-hit" theory was proposed that included the induction of CD80 (B7-1) and regulatory T-cell (Treg) dysfunction, with or without impaired autoregulatory functions of the podocyte. In contrast to the well-established involvement of T cells, the role of B cells has not been clearly identified. However, B-cell biology has recently gained more attention, because rituximab (a monoclonal antibody directed against CD20-bearing cells) demonstrated a very good therapeutic response in the treatment of childhood and adult MCNS. Here, we discuss recent insights into the pathogenesis of MCNS in children.

Ethanol extract of Plantago asiatica L. controls intracellular fat accumulation and lipid metabolism in 3T3-L1 Adipocytes (차전초의 에탄올추출물이 3T3-L1 지방세포의 지방축적 및 지질대사에 미치는 영향)

  • Jeon, Seo Young;Park, Ji Young;Shin, Insoon;Kim, Sung Ok;An, Hee Duk;Kim, Mi Ryeo
    • The Korea Journal of Herbology
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    • v.29 no.4
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    • pp.77-82
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    • 2014
  • Objectives : The effects of ethanol extract of Plantago asiatica L. were investgated on adipocyte differentiation, lipopogenesis, lipolysis and apoptosis using differnentiated 3T3-L1 adipocytes. Methods : Plantago asiatica L. was extracted with ethanol (CCE). We carried on MTT assay for cell proliferation, Oil Red O staining for determination of cell differentiation and intracelluar adipogenesis. TUNEL staining assay for cell apoptosis, and Western blot analysis for measurement of pAMPK and pACC, $C/EBP{\alpha}$, $PPAR{\gamma}$ protein expressions were performed. Results : The addition of CCE up to 0.2 mg/ml into cell culture media showed no cytotoxicity. Treatment of 0.2 mg/ml CCE significantly inhibited differentiation in 3T3-L1 preadipocytes. Lipid accumulation of the CCE treated cells was decreased compared with that of control. Induction of cell apoptosis was increased in CCE treated cells compared with that of control. AMPK and ACC levels of the cells with 0.2 mg/ml CCE were led to phosphorylation and also expressions of $C/EBP{\alpha}$ and $PPAR{\gamma}$, as adipogenic transcription factors, were suppressed compared with those of control. Conclusions : Taken together, these results provide evidence that CCE has a regulatory role in lipid metabolism that is related to differentiation into adipocytes, adipogenesis and apoptosis.

Anti-Obesity Effect of Ethyl Acetate Fraction from 50% Ethanol Extract of Fermented Curcuma longa L. in 3T3-L1 Cells (발효울금 주정추출물부터 분리된 에틸아세테이트 분획물에 대한 3T3-L1 세포에서의 지방 형성 억제 효과)

  • Kim, Jihye;Park, Jeongjin;Jun, Woojin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.11
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    • pp.1681-1687
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    • 2014
  • In the present study, we investigated the effect of ethyl acetate fraction from 50% ethanol extract of fermented Curcuma longa L. (FCEE) on lipid metabolism in 3T3-L1 cells. The safety range of FCEE was up to $300{\mu}g/mL$. Effects of FCEE on lipid accumulation and intracellular triglyceride (TG) content in 3T3-L1 cells were examined by Oil Red O staining and AdipoRed assay. Compared to adipocytes, lipid accumulation and intracellular TG content were significantly reduced by 10.2% and 13.7%, respectively, upon FCEE treatment at a concentration of $200{\mu}g/mL$. Glucose uptake by 3T3-L1 cells was significantly reduced by 36.6% compared to adipocytes at a concentration of $200{\mu}g/mL$. On day 8, free glycerol release into the culture medium was significantly reduced compared to adipocytes at concentrations of 50, 100, and $200{\mu}g/mL$ of FCEE. FCEE significantly stimulated RNA expression of AMP-activated protein kinase (AMPK) and suppressed mRNA expressions of sterol regulatory element-binding protein-1c (SREBP-1c), CCAAT/enhancer binding proteins ${\alpha}$ ($C/EBP{\alpha}$), and peroxisome proliferator- activated receptor ${\gamma}$ ($PPAR{\gamma}$) in 3T3-L1 cells. These results suggest that FCEE inhibits adipogenesis through activation of AMPK mRNA expressions and inhibition of SREBP-1c, $C/EBP{\alpha}$, and $PPAR{\gamma}$ mRNA expressions.

Proteasome Function Is Inhibited by Polyglutamine-expanded Ataxin-1, the SCA1 Gene Product

  • Park, Yongjae;Hong, Sunghoi;Kim, Sung-Jo;Kang, Seongman
    • Molecules and Cells
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    • v.19 no.1
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    • pp.23-30
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    • 2005
  • Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder caused by expansion of the polyglutamine tract in the SCA1 gene product, ataxin-1. Using d2EGFP, a short-lived enhanced green fluorescent protein, we investigated whether polyglutamine-expanded ataxin-1 affects the function of the proteasome, a cellular multicatalytic protease that degrades most misfolded proteins and regulatory proteins. In Western blot analysis and immunofluorescence experiments, d2EGFP was less degraded in HEK 293T cells transfected with ataxin-1(82Q) than in cells transfected with lacZ or empty vector controls. To test whether the stability of the d2EGFP protein was due to aggregation of ataxin-1, we constructed a plasmid carrying $ataxin-1-{\Delta}114$, lacking the self-association region (SAR), and examined degradation of the d2EGFP. Both the level of $ataxin-1-{\Delta}114$ aggregates and the amount of d2EGFP were drastically reduced in cells containing $ataxin-1-{\Delta}114$. Furthermore, d2EGFP localization experiments showed that polyglutamine-expanded ataxin-1 inhibited the general function of the proteasome activity. Taken together, these results demonstrate that polyglutamine-expanded ataxin-1 decreases the activity of the proteasome, implying that a disturbance in the ubiquitin-proteasome pathway is directly involved in the development of spinocerebellar ataxia type1.

Roles of RUNX1 and PU.1 in CCR3 Transcription

  • Su-Kang Kong;Byung Soo Kim;Sae Mi Hwang;Hyune Hwan Lee;Il Yup Chung
    • IMMUNE NETWORK
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    • v.16 no.3
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    • pp.176-182
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    • 2016
  • CCR3 is a chemokine receptor that mediates the accumulation of allergic inflammatory cells, including eosinophils and Th2 cells, at inflamed sites. The regulatory sequence of the CCR3 gene, contains two Runt-related transcription factor (RUNX) 1 sites and two PU.1 sites, in addition to a functional GATA site for transactivation of the CCR3 gene. In the present study, we examined the effects of the cis-acting elements of RUNX1 and PU.1 on transcription of the gene in EoL-1 eosinophilic cells and Jurkat T cells, both of which expressed functional surface CCR3 and these two transcription factors. Introduction of RUNX1 siRNA or PU.1 siRNA resulted in a modest decrease in CCR3 reporter activity in both cell types, compared with transfection of GATA-1 siRNA. Cotransfection of the two siRNAs led to inhibition in an additive manner. EMSA analysis showed that RUNX1, in particular, bound to its binding motifs. Mutagenesis analysis revealed that all point mutants lacking RUNX1- and PU.1-binding sites exhibited reduced reporter activities. These results suggest that RUNX1 and PU.1 participate in transcriptional regulation of the CCR3 gene.