• 대한의생명과학회지
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• 제29권3호
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• pp.137-143
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• 2023

Inflammation plays an important role in immune system's response to tissue injury and biological stimuli. However, excessive inflammation can cause tissue damage. Therefore, the development of naturally derived anti-inflammatory agents have received broad attention. In this study, we investigated the anti-inflammatory mechanism of Rubi Fructus (RF) extract on the mast cell-mediated inflammatory response. To determine the regulatory mechanism of RF in inflammatory reaction, we evaluated the effects of RF on secretion of interleukin (IL)-8, IL-6 and tumor necrosis factor (TNF)-α and activation of nuclear factor-κB (NF-κB) and caspase-1 in activated human mast cells-1 (HMC-1). The results showed that RF attenuated IL-8, IL-6 and TNF-α secretion in a concentration-dependent manner. Moreover, RF significantly attenuated caspase-1and NF-κB activation in activated HMC-1. Conclusively, the present results provide evidence that RF may be a promising agent for anti-inflammatory therapy.

• 대한의생명과학회지
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• 제21권4호
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• pp.172-180
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• 2015

It is well reported that tumor cells can regulate host immune systems. To identify the detailed changes of immune cells between tumor bearing mice and normal mice, we evaluated the systemic immune cell phenotype of B16F10 tumor bearing mice in a time dependent manner. The lymphocytic population (CD4+ and CD8+ T cells) of tumor bearing mice significantly decreased compared to that of normal mice. We found that the Foxp3+CD25+ CD4 T cell decreased, but the Foxp3+$CD25^{high}$ CD4 T cell significantly increased. All subpopulations of CD8 T cells decreased, except the CD62L-CD44+ CD8 T cell subpopulation. The myeloid cell population (CD11b+ and Gr-1+ cells) of tumor bearing mice significantly increased. Specifically, Foxp3+$CD25^{high}$ CD4 T cell and CD11b+Gr-1+ cells significantly increased in early phase of tumor progression. These results are helpful to understand the change of the systemic immune cell subpopulation of tumor bearing mice in a time-dependent manner.

• BMB Reports
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• 제50권1호
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• pp.25-30
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• 2017

In the central nervous system, viral infection can induce inflammation by up-regulating pro-inflammatory mediators that contribute to enhanced infiltration of immune cells into the central nervous areas. Celastrol is known to exert various regulatory functions, including anti-microbial activities. In this study, we investigated the regulatory effects and the mechanisms of action of celastrol against astrocytes activated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, as a model of pro-inflammatory mediated responses. Celastrol significantly inhibited poly(I:C)-induced expression of adhesion molecules, such as ICAM-1/VCAM-1, and chemokines, such as CCL2, CXCL8, and CXCL10, in CRT-MG human astroglioma cells. In addition, celastrol significantly suppressed poly(I:C)-induced activation of JNK MAPK and STAT1 signaling pathways. Furthermore, celastrol significantly suppressed poly(I:C)-induced activation of the $NF-{\kappa}B$ signaling pathway. These results suggest that celastrol may exert its regulatory activity by inhibiting poly(I:C)-induced expression of pro-inflammatory mediators by suppressing activation of JNK MAPK-STAT1/$NF-{\kappa}B$ in astrocytes.

• The Korean Journal of Physiology and Pharmacology
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• 제27권5호
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• pp.427-436
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• 2023

Mitotic arrest deficient 2 like 2 (Mad2L2, also known as Mad2B), the human homologue of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares high sequence homology with Mad2, the mitotic checkpoint protein. Previously, we demonstrated the involvement of Mad2B in the cisplatin-induced DNA damage response. In this study, we extend our findings to show that Mad2B is recruited to sites of DNA damage in human cancer cells in response to cisplatin treatment. We found that in undamaged cells, Mad2B exists in a complex with Polζ-Rev1 and the APC/C subunit Cdc27. Following cisplatin-induced DNA damage, we observed an increase in the recruitment of Mad2B and Cdc20 (the activators of the APC/C), to the complex. The involvement of Mad2B-Cdc20-APC/C during DNA damage has not been reported before and suggests that the APC/C is activated following cisplatin-induced DNA damage. Using an in vitro ubiquitination assay, our data confirmed Mad2B-dependent activation of APC/C in cisplatin-treated cells. Mad2B may act as an accelerator for APC/C activation during DNA damage response. Our data strongly suggest a role for Mad2B-APC/C-Cdc20 in the ubiquitination of proteins involved in the DNA damage response.

• Gut and Liver
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• 제12권6호
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• pp.664-673
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• 2018

Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. Methods: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was decreased, but that of CD11b, IL-10, and transforming growth factor-${\beta}$ (TGF-${\beta}$) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-${\alpha}$, and IFN-${\gamma}$ decreased, but that of IL-10, TGF-${\beta}$, and Foxp3 increased in the MSC- and MSC-DC-injected groups. Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.

• BMB Reports
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• 제50권9호
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• pp.437-444
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• 2017

Different types of eukaryotic cells may adopt seemingly distinct modes of directional cell migration. However, several core aspects are regarded common whether the movement is either ameoboidal or mesenchymal. The region of cells facing the attractive signal is often termed leading edge where lamellipodial structures dominates and the other end of the cell called rear end is often mediating cytoskeletal F-actin contraction involving Myosin-II. Dynamic remodeling of cell-to-matrix adhesion involving integrin is also evident in many types of migrating cells. All these three aspects of cell migration are significantly affected by signaling networks of TorC2, TorC1, and PP2A/B56. Here we review the current views of the mechanistic understanding of these regulatory signaling networks and how these networks affect eukaryotic cell migration.

• Clinical and Experimental Pediatrics
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• 제50권12호
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• pp.1165-1172
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• 2007

Self/non-self discrimination and unresponsiveness to self is the fundamental properties of the immune system. Self-tolerance is a state in which the individual is incapable of developing an immune response to an individual's own antigens and it underlies the ability to remain tolerant of individual's own tissue components. Several mechanisms have been postulated to explain the tolerant state. They can be broadly classified into two groups: central tolerance and peripheral tolerance. Several mechanisms exist, some of which are shared between T cells and B cells. In central tolerance, the recognition of self-antigen by lymphocytes in bone marrow or thymus during development is required, resulting in receptor editing (revision), clonal deletion, anergy or generation of regulatory T cells. Not all self-reactive B or T cells are centrally purged from the repertoire. Additional mechanisms of peripheral tolerance are required, such as anergy, suppression, deletion or clonal ignorance. Tolerance is antigen specific. Generating and maintaining the self-tolerance for T cells and B cells are complex. Failure of self-tolerance results in immune responses against self-antigens. Such reactions are called autoimmunity and may give rise to autoimmune diseases. Development of autoimmune disease is affected by properties of the genes of the individual and the environment, both infectious and non-infectious. The host's genes affect its susceptibility to autoimmunity and the environmental factors promote the activation of self-reactive lymphocytes, developing the autoimmunity. The changes in participating antigens (epitope spreading), cells, cytokines or other inflammatory mediators contribute to the progress from initial activation to a chronic state of autoimmune diseases.

• Molecules and Cells
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• 제38권10호
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• pp.895-903
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• 2015

Non-coding microRNAs (miRNAs) regulate the translation of target messenger RNAs (mRNAs) involved in the growth and development of a variety of cells, including primordial germ cells (PGCs) which play an essential role in germ cell development. However, the target mRNAs and the regulatory networks influenced by miRNAs in PGCs remain unclear. Here, we demonstrate a novel miRNAs control PGC development through targeting mRNAs involved in various cellular pathways. We reveal the PGC-enriched expression patterns of nine miRNAs, including miR-10b, -18a, -93, -106b, -126-3p, -127, -181a, -181b, and -301, using miRNA expression analysis along with mRNA microarray analysis in PGCs, embryonic gonads, and postnatal testes. These miRNAs are highly expressed in PGCs, as demonstrated by Northern blotting, miRNA in situ hybridization assay, and miRNA qPCR analysis. This integrative study utilizing mRNA microarray analysis and miRNA target prediction demonstrates the regulatory networks through which these miRNAs regulate their potential target genes during PGC development. The elucidated networks of miRNAs disclose a coordinated molecular mechanism by which these miRNAs regulate distinct cellular pathways in PGCs that determine germ cell development.

• Animal cells and systems
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• 제2권2호
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• pp.249-258
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• 1998

Obesity, one of the most common metabolic diseases in industrial countries is characterized by an increase in the number or size of adipocytes. In an effort to create transgenic mouse models for the study of obesity we developed a novel technique in which adipose tissue can be ablated genetically at will, at any specific developmental stage and/or physiological condition, by the treatment of ganciclovir. We made a series of adipocytespecific expression vectors using minimal regulatory regions of brown adipocyte-specific uncoupling protein (UCP-1) gene and adipocyte-specific aP2 gene, and then analyzed their expression characteristics in cultured cell lines. When both constructs pUCP-LacZ and paP2-LacZ were transfected transiently into differentiating 3T3-L1 (pre-while adipocytes) and HIB-1B (pre-brown adipocytes) cell lines in vitro and then monitored by X-gal staining of cells, these regulatory regions were sufficient to show proper differentiation stage-specific expression in adipocvtes. To confirm that adipocytes expressing HSV-TK controlled by these minimal requlatory elements are sufficient to kill themselves with ganciclovir treatment pUCP-TK and paP2-TK expression constructs were transfected stably into HIB-1B and 3T3-L1 cells, respectively, and their ganciclovir sensitivities were tested during in vitro differentiation of cells. As expected more than 80% of cells were dead by the 7th day of treatment with ganciclovir while negative control cells were not affected at all. The data suqqest that the constructed vectors are suitable for obtaining novel obese transqenic models based on a conditional genetic tissue ablation method.

• IMMUNE NETWORK
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• 제15권1호
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• pp.16-26
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• 2015

The female reproductive tract has two main functions: protection against microbial challenge and maintenance of pregnancy to term. The upper reproductive tract comprises the fallopian tubes and the uterus, including the endocervix, and the lower tract consists of the ectocervix and the vagina. Immune cells residing in the reproductive tract play contradictory roles: they maintain immunity against vaginal pathogens in the lower tract and establish immune tolerance for sperm and an embryo/fetus in the upper tract. The immune system is significantly influenced by sex steroid hormones, although leukocytes in the reproductive tract lack receptors for estrogen and progesterone. The leukocytes in the reproductive tract are distributed in either an aggregated or a dispersed form in the epithelial layer, lamina propria, and stroma. Even though immune cells are differentially distributed in each organ of the reproductive tract, the predominant immune cells are T cells, macrophages/dendritic cells, natural killer (NK) cells, neutrophils, and mast cells. B cells are rare in the female reproductive tract. NK cells in the endometrium significantly expand in the late secretory phase and further increase their number during early pregnancy. It is evident that NK cells and regulatory T (Treg) cells are extremely important in decidual angiogenesis, trophoblast migration, and immune tolerance during pregnancy. Dysregulation of endometrial/decidual immune cells is strongly related to infertility, miscarriage, and other obstetric complications. Understanding the immune system of the female reproductive tract will significantly contribute to women's health and to success in pregnancy.