• IMMUNE NETWORK
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• 제6권4호
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• pp.199-203
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• 2006

Background: Eckol purified from Ecklonia cava, a brown alga has been known to have cytoprotective effects on some cell lines against oxidants and ionizing radiation. However, there is no study about the effects of eckol on immune cells. Methods: Bone marrow (BM)-derived dendritic cells (DCs) were used to demonstrate the immunomodulatory effects of eckol on DCs, such as viability, the expression of surface markers, allogeneic stimulating capacity using MTI, flow cytometric, $^3H$-thymidine incorporation assay. Results: Eckol did protect DCs against cytokine withdrawal-induced apoptosis in a concentration dependent manner based on MTT assay. And also, it increased the expression of MHC class II and CD86 (B7.2) molecules, maturation markers, on the surface of viable DCs gated in FACS analysis. Furthermore, eckol-treated DCs stimulated the proliferation of allogeneic $CD4^+$ T lymphocytes compared to imDCs in $^3H$-thymidine incorporation assay. $CD4^+$ T lymphocytes activated with eckol-treated DCs produced the larger amount of IFN-${\gamma}$ and IL-4 than those cells with imDCs. Conclusion: Taken together, we demonstrate in this study that eckol, a pure compound of Ecklonia cava, may modulate the immune responses through the phenotypic and functional changes of DCs.

• Parasites, Hosts and Diseases
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• 제61권2호
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• pp.138-146
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• 2023

Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses. Dendritic cells (DCs) are the most prominent type of antigen-presenting cells and regulate the host immune response, including the response of T-cells. However, differences in the DC responses of these mouse strains to T. gondii infection have yet to be characterized. In this study, we cultured bone marrow-derived DCs (BMDCs) from BALB/c and C57BL/6 mice. These cells were infected with T. gondii. The activation of the BMDCs was assessed based on the expression of cell surface markers and cytokines. In the BMDCs of both mouse strains, we detected significant increases in the expression of cell surface T-cell co-stimulatory molecules (major histocompatibility complex (MHC) II, CD40, CD80, and CD86) and cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12p40, IL-1β, and IL-10) from 3 h post-T. gondii infection. The expression of MHC II, CD40, CD80, CD86, IFN-γ, IL-12p40, and IL-1β was significantly higher in the T. gondii-infected BMDCs obtained from the C57BL/6 mice than in those from the BALB/c mice. These findings indicate that differences in the activation status of the BMDCs in the BALB/c and C57BL/6 mice may account for their differential susceptibility to T. gondii.

• 생명과학회지
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• 제16권5호
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• pp.759-766
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• 2006

급성 전골수성 백혈병은 염색체 전위의 결과로 생긴 PML/RAR$({\alpha})$ 융합 단백의 과발현으로 영향을 받은 전골 수세포의 분화 정지로 발생하는 골수성 백혈병의 일종이다. 삼산화 비소는 세포고사를 유발하여 급성전골수성 백혈병의 관해를 유도한다는 것이 밝혀졌으나 이 약제에 대한 감수성이 다양하여 고형암에 적용하기에는 제한점이 있다. All-trans-retinoic acid (ATRA)에 감수성인 NB4 세포주와 내성인 UF-1 세포주 모두에 삼산화 비소가 세포고사를 유도하였다. 백혈병 세포주를 삼산화 비소로 처리하여, 세포내 GSH 농도가 낮아지고 세포고사의 감수성이 높아지는 상관관계를 찾았으며 전골수성 암세포를 수지상 세포 표면 표식자를 가진 세포로 분화시켰다. ATRA에 대한 감수성인 세포주와 내성인 세포주의 삼산화 비소에 대한 반응의 차이를 이해하고, 전골수 세포가 수지상 세포로 분화하는 과정을 규명한다면, 삼산화 비소에 의한 전골수성 백혈병의 완전관해의 기전을 밝힐 수 있고 또한 임상적용을 확대할 수 있을 것이다.

• IMMUNE NETWORK
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• 제16권1호
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• pp.75-84
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• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

• 대한수의학회지
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• 제54권3호
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• pp.139-146
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• 2014

Jeotgal (salted seafood) has been one of major fermented foods in Korea for long time. Although there are many studies about Jeotgal in various aspects of food, its immunological importance on hosts has not been elucidated yet. In this study, we investigated if several bacteria isolated from Jeotgal may modulate the function of dendritic cells (DCs), powerful antigen-presenting cells equipped with special immunological capabilities. 4 Jeotgal bacteria were selected as representatives and used for experiments. To treat viable DCs, those bacteria were killed at $60^{\circ}C$ for 30 min. The viability of DCs treated with Jeotgal bacteria was verified and two isolates significantly induced high production of interleukin-12, a representative cell-mediated cytokine of DCs. Surface activation and maturation markers (MHC class II, CD40, CD86) of DCs were analyzed by flow cytometer. In addition, the treated DCs showed significantly high lymphocyte stimulatory capability compared to control DCs based on allogeneic mixed lymphocyte reactions. These observations suggest that Jeotgal isolates can function as immunostimulating bacteria in hosts, like Lactobacillus. Taken together, these experimental evidences may broaden the use of Jeotgal isolates in immunological fields in addition to as a fermented food.

• The Korean Journal of Physiology and Pharmacology
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• 제21권3호
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• pp.301-308
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• 2017

27-Hydroxycholesterol induces differentiation of monocytic cells into mature dendritic cells, mDCs. In the current study we sought to determine roles of the PI3K and the ERK pathways in the 27OHChol-induced differentiation. Up-regulation of mDC-specific markers like CD80, CD83 and CD88 induced by stimulation with 27OHChol was significantly reduced in the presence of LY294002, an inhibitor of PI3K, and U0126, an inhibitor of ERK. Surface expression of MHC class I and II molecules elevated by 27OHChol was decreased to basal levels in the presence of the inhibitors. Treatment with LY294002 or U0126 resulted in recovery of endocytic activity which was reduced by 27OHChol. CD197 expression and cell adherence enhanced by 27OHChol were attenuated in the presence of the inhibitors. Transcription and surface expression of CD molecules involved in atherosclerosis such as CD105, CD137 and CD166 were also significantly decreased by treatment with LY294002 and U0126. These results mean that the PI3K and the ERK signaling pathways are necessary for differentiation of monocytic cells into mDCs and involved in over-expression of atherosclerosis-associated molecules in response to 27OHChol.

• 한국식품과학회지
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• 제49권5호
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• pp.559-566
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• 2017

본 연구는 자소엽 조다당 추출물(PCP)의 면역활성에 관하여 알아보기 위하여, 선천면역계의 대표적인 면역세포인 수지상세포 및 후천면역계의 대표적인 면역세포인 비장세포에 PCP를 처리하여 면역세포의 면역활성능에 관하여 측정하였다. 수지상세포에 PCP를 1, 5 및 $10{\mu}g/mL$의 농도를 처리한 결과, 세포생존율이 $103.4{\pm}3.8$, $108.8{\pm}2.1$, $117.8{\pm}3.3%$ (n =3)로 나타나 세포독성을 유발하지 않았으며, 주요 면역활성 인자인 산화질소의 분비능을 관찰한 결과, 각각 $2.7{\pm}0.2$, $4.5{\pm}0.2$, $7.3{\pm}0.3{\mu}M$ (n =3)로 농도 의존적으로 나타났다. 농도(1, 5 및 $10{\mu}g/mL$)별 PCP 처리구에서 사이토카인의 분비능을 관찰한 결과, TNF-${\alpha}$ ($372.3{\pm}0.32$, $604.8{\pm}0.54$ 및 $954.2{\pm}1.32pg/mL$), IL-6 ($508.4{\pm}0.39$, $761.5{\pm}1.34$ 및 $1038.5{\pm}1.67pg/mL$), IL-$1{\beta}$ ($314.5{\pm}1.04$, $524.8{\pm}1.89$ 및 $664.8{\pm}0.89pg/mL$), IL-12 ($321.4{\pm}0.94$, $832.5{\pm}0.85$ 및 $901.{\pm}0.94pg/mL$)가 유의적으로 증가되는 것으로 관찰되었다. 또한 후천면역에서 중요한 역할을 수행하는 면역 T 세포가 다량으로 분포하는 비장 조직으로부터 비장세포를 분리하여 PCP를 처리하였을 때, 세포 증식능이 유의적으로 증가하였으며, 면역활성을 유도하는 Th1 세포가 분비하는 사이토카인의 함량 또한 유의적으로 증가되는 것으로 나타났다. 이러한 결과로 미루어 볼 때 PCP의 처리는 선천면역뿐만 아니라 후천면역에 관여하는 다양한 면역세포의 활성화에 직간접적으로 관여하는 것으로 사료된다. 본 연구는 자소엽조다당 추출물의 면역활성 유도 효과에 관한 가능성을 제시하였고, 향후 자소엽 조다당 추출물을 분리 및 정제과정을 통하여 구조분석 및 정제된 조다당 추출물의 정확한 면역활성과 면역활성기전에 관한 면밀한 연구가 필요할 것으로 사료된다.

• 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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• 제45권9호
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• pp.538-543
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• 2012

We evaluated the expression of the costimulatory molecules CD80 and CD83 and major histocompatibility (MHC) class II induced by 2,4-dinitrofluorobenzene (DNFB) in the RAW 264.7 macrophage cell line. In contrast to the previously reported effect of DNFB on dendritic cells, CD86 expression did not change. Furthermore, we observed that the CD83 expression level transiently increased and then decreased. Induction of CD80 and MHC class II molecule expression and a decrease in CD83 expression by DNFB in vitro were also confirmed in splenocytes of BALB/c and NC/Nga mice. However, DNFB did not influence CD83 expression in peritoneal $CD11b^+$ cells from BALB/c or NC/Nga mice. Detailed in vivo experiments and further studies on the possible contribution of $CD11b^+$ cells to induce atopic dermatitis (AD) would be helpful to attain a better understanding of AD pathogenesis.

• 생명과학회지
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• 제19권12호
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• pp.1690-1697
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• 2009

CD11c와 CD80 및 CD86과 같은 보조 수용체는 주로 수지상 세포에서 발현되는 세포 표지 인자이다. 본 연구에서는 KG-1, HL-60, NB4 및 THP-1 세포와 같은 여러 종류의 백혈병 세포를 이용하여 이들 세포에 재조합 Flt-3 리간드를 처리하였을 때 수지상 세포의 표면 인자인 CD11c의 발현에 어떠한 변화가 있는가를 조사하였다. KG-1 세포뿐만 아니라 NB4세포와 HL-60 세포에서도 Flt-3 수용체가 발현됨을 확인하였으나 THP-1 세포에서는 이들 수용체가 발현되지 않았다. KG-1 세포를 Flt-3 리간드나 granulocyte macrophage-colony stimulating factor (GM-CSF)와 tumor necrosis factor (TNF)-$\alpha$를 섞은 배양액에서 배양하였을 때 세포 증식은 억제되었으며 CD11c 발현은 현저히 증가되었다. 그러나 Flt-3 리간드를 처리한 KG-1세포에서는 GM-CSF와 TNF-$\alpha$를 처리한 세포에서와는 다르게 major histocompatibility complex (MHC)-I 및 MHC-II의 발현은 증가되지 않았다. Flt-3 리간드는 HL-60 세포와 NB4 세포의 CD11c 발현도 증가시켰으나 THP-1 세포에서는 아무런 영향이 없었다. CD11c의 발현과 비교하여 CD11b의 발현은 Flt-3 리간드에 의하여 KG-1 세포에서는 약하게 증가하였으나 NB4 세포와 HL-60 세포에서는 증가되지 않았다. KG-1 세포를 Flt-3 리간드로 처리하였을 때 extracellular signal-regulated kinase-1/2 (ERK-1/2)와 p38-mitogen-activated protein kinase (p38-MAPK)의 단백질 인산화가 증가되었으며 Flt-3 리간드에 의한 CD11c 발현의 증가는 MEK의 억제제인PD98059에 의하여 사라짐을 확인하였다. 본 연구 결과는 Flt-3 수용체 리간드의 처리에 의하여 $CD34^+$ myelomonocyte분화 단계인 KG-1 세포와 promyelocyte 분화 단계의 백혈병 세포에서 수지상 세포와 유사한 세포 형으로 분화된다는 것을 보였고 Flt-3 수용체 리간드에 의한 이들 백혈병 세포의 수지상 세포유사 세포로의 분화는 ERK-1/2의 활성화에 의하여 일어날 수 있음을 보여 준다.