• IMMUNE NETWORK
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• v.12 no.6
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• pp.247-252
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• 2012

Pancreatic cancer is the fourth commonest cause of cancer-related deaths in the world. However, no adequate therapy for pancreatic cancer has yet been found. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against the human pancreatic cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3 for 14 days. The resulting populations of CIK cells comprised 94% $CD3^+$, 4% $CD3^-CD56^+$, 41% $CD3^+CD56^+$, 11% $CD4^+$, and 73% $CD8^+$. This heterogeneous cell population was called cytokine-induced killer (CIK) cells. At an effector-target cell ratio of 100 : 1, CIK cells destroyed 51% of AsPC-1 human pancreatic cancer cells, as measured by the $^{51}Cr$-release assay. In addition, CIK cells at doses of 3 and 10 million cells per mouse inhibited 42% and 70% of AsPC-1 tumor growth in nude mouse xenograft assays, respectively. This study suggests that CIK cells may be used as an adoptive immunotherapy for pancreatic cancer patients.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1106-1115
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• 2009

Mori Ramulus has multiple applications in Korean traditional medicine prescription because it has antioxidant and anti-inflammatory effects by reducing macrophage activities. Yet, no studies on the anti-arthritic activity of EMR (extract of Mori Ramulus) have been reported in vitro and in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Because collagen-induced arthritis (CIA) is similar to RA in pathological symptoms and immune reactions, there have been several reports concerning RA using CIA mouse model. Here, we investigated the effects of Mori Ramulus on RA using CIA mice. The importance of CD4+ Th1 cells in RA progress was previously indicated and studies further showed that Th17 cells play a prime role in severity of disease. Accordingly, the present study was focused on CIA associated with CD4+ Th1 cells and Th1 7 cells. DBA/1OlaHsd mice were immunized with bovine type II collagen (CII). After a second collagen immunization, mice were treated with EMR once a day for 4 weeks. The severity of arthritis within the paw joints was evaluated by histological assessment of cartilage destruction and pannus formation. Immune cells in peripheral blood mononuclear cells (PBMC), draining lymph node (DLN) and paw joints, cytokine production and gene expression were assessed from CIA mouse using ELISA, FACS and real-time PCR analysis. Administration of EMR significantly suppressed the progression of CIA and inhibited the production of TNF-$\alpha$, IL-6 and IL-17 in the serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with EMR. In conclusion, our results demonstrate that EMR significantly suppressed the progression of CIA and that this action was mediated by the decreased production of TNF-$\alpha$, IL-6, IL-17 and collagen II-specific antibody in the serum. EMR suppressed Th17 cells and reduced level of IL-6 via B cell suppression, and thus, the levels of autoantibodies produced from B cells were decreased. Furthermore, EMR suppressed NKT cells which directly stimulate B cells and develop imbalance of Th1/Th2 cell. Oral administration of EMR (100 mg/kg or 200 mg/kg) significantly suppressed the progression of CIA, which is comparable to that of methotrexate (MTX, 0.3 mg/kg) used as a positive control. We are currently studying the mechanism underlying the therapeutic role for EMR in CIA mice.

• Development and Reproduction
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• v.17 no.4
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• pp.441-449
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• 2013

Recent study showed that T cells in the immune organs and peripheral blood are influenced by estradiol, leading to a dysfunction of the immune system. However, little is known about the thymic-gonadal relationship during the estrous cycle in mouse. Therefore, the purpose of this study was to elucidate the mechanism by which a change in estradiol levels during the estrous cycle regulates the development of T cells in the mouse thymus. Six-week-old ICR mice were used and divided into four groups, including diestrous, proestrous, estrous, and metestrous. We first confirmed that ER-${\alpha}$ and - ${\beta}$ estrogen receptors were expressed in thymic epithelial cells, showing that their expression was not different during the estrous cycle. There was also no significant difference in thymic weight and total number of thymocytes during the estrous cycle. To determine the degree of thymocyte differentiation during the estrous cycle, we analyzed thymocytes by flow cytometry. As a result, the percentage of CD4+CD8+ double-positive (DP) T cells was significantly decreased in the proestrous phase compared to the diestrous phase. However, CD4+CD8- or CD4-CD8+ (SP) T cells were significantly increased in the proestrous phase compared to the diestrous phase. In addition, the percentage of CD44+CD25- (DN1) T cells was significantly decreased in the estrous phase compared to other phases, whereas the percentages of CD44+CD25+ (DN2), CD44-CD25+ (DN3), and CD44-CD25- (DN4) were not changed during the estrous cycle. These results indicate that the development of thymocytes may arrest in the DP to SP transition stage in the proestrous phase displaying the highest serum level of estradiol. This study suggests that a change in estradiol levels during the estrous cycle may be involved in the regulation of thymocyte differentiation in the mouse thymus.

• Parasites, Hosts and Diseases
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• v.61 no.2
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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.

• Journal of Microbiology and Biotechnology
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• v.28 no.2
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• pp.218-226
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• 2018

Nanometric Lactobacillus plantarum nF1 (nLp-nF1) is a biogenics consisting of dead L. plantarum cells pretreated with heat and a nanodispersion process. In this study, we investigated the immune-enhancing effects of nLp-nF1 in vivo and in vitro. To evaluate the immunostimulatory effects of nLp-nF1, mice immunosuppressed by cyclophosphamide (CPP) treatment were administered with nLp-nF1. As expected, CPP restricted the immune response of mice, whereas oral administration of nLp-nF1 significantly increased the total IgG in the serum, and cytokine production (interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-${\alpha}$)) in bone marrow cells. Furthermore, nLp-nF1 enhanced the production of splenic cytokines such as IL-12, TNF-${\alpha}$, and interferon gamma (IFN-${\gamma}$). In vitro, nLp-nF1 stimulated the immune response by enhancing the production of cytokines such as IL-12, TNF-${\alpha}$, and IFN-${\gamma}$. Moreover, nLp-nF1 given a food additive enhanced the immune responses when combined with various food materials in vitro. These results suggest that nLp-nF1 could be used to strengthen the immune system and recover normal immunity in people with a weak immune system, such as children, the elderly, and patients.

• IMMUNE NETWORK
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• v.20 no.6
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• pp.51.1-51.17
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• 2020

Respiratory syncytial virus (RSV) causes severe pulmonary disease in infants, young children, and the elderly. Formalin inactivated RSV (FI-RSV) vaccine trials failed due to vaccine enhanced respiratory disease, but the underlying immune mechanisms remain not fully understood. In this study, we have used wild type C57BL/6 and CD4 knockout (CD4KO) mouse models to better understand the roles of the CD4 T cells and cellular mechanisms responsible for enhanced respiratory disease after FI-RSV vaccination and RSV infection. Less eosinophil infiltration and lower pro-inflammatory cytokine production were observed in FI-RSV vaccinated CD4KO mice after RSV infection compared to FI-RSV vaccinated C57BL/6 mice. NK cells and cytokine-producing CD8 T cells were recruited at high levels in the airways of CD4KO mice, correlating with reduced respiratory disease. Depletion studies provided evidence that virus control was primarily mediated by NK cells whereas CD8 T cells contributed to IFN-γ production and less eosinophilic lung inflammation. This study demonstrated the differential roles of effector CD4 and CD8 T cells as well as NK cells, in networking with other inflammatory infiltrates in RSV disease in immune competent and CD4-deficient condition.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.2
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• pp.34-45
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• 2014

Objectives: This study was designed to investigate intestinal immune system activation and antimetastatic effect of Ojeok-san on cancer cells by oral administration. Methods: Cell viability of Ojeok-san was tested with colon 26-M3.1 carcinoma cells and Peyer's patch cells in vitro. Antimetastatic experiments were conducted in vivo mouse model by using colon 26-M3.1 carcinoma cell. To observe immunomodulating effects of Ojeok-san on Peyer's patch cells, we measured interleukin (IL)-4, GM-CSF. In addition to observing effects of Ojeok-san on hematopoiesis, we measured proliferation of bone marrow cells mediated by Peyer's patch cells in vitro. IgA induction activated in serum and intestinal content was measured to observe the effect of orally administered Ojeok-san on mucosal immune system. After administering Ovalbumin (OVA) with Ojeok-san, Proliferation of Peyer's patch cell was measured to investigate gut immunostimulatory effect. Results: in vitro cytotoxicity analysis, the inhibitory concentration $(IC)_{50}$ of the colon 26-M3.1 carcinoma cell was $890{\mu}g/ml$. $IC_{50}$ of the Peyer's patch cells with LPS was $990{\mu}g/ml$. We found that orally administered Ojeok-san significantly inhibited tumor metastasis in vivo. In addition, the amounts of IL-4 and GM-CSF in the culture supernatant of Peyer's patch cells were significantly increased compared to the control group. The proliferation of bone marrow cell was significantly up-regulated with Ojeok-san. These results indicate that oral administration of Ojeok-san enhances the secretion of hematopoietic growth factors such as GM-CSF and IL-4 from Peyer's patch cells, and these cytokines also act on modulator of bone marrow cell proliferation. After orally administering Ovalbumin (OVA) with Ojeok-san, IgA induction and Proliferation of peyer's patch cell was up-regulated with Ojeok-san. These results means orally administered Ojeok-san activates intestinal immune system and has an inhibitory effect on tumor metastasis. Conclusions: Orally administered Ojeok-san appears to have considerable activity on the anti-metastasis by activation of immune system.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.104-112
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• 2012

Silica is one of the most abundant compounds found in nature. Immoderate exposure to crystalline silica has been linked to pulmonary disease and crystalline silica has been classified as a Group I carcinogen. Ultrafine (diameter <100 nm) silica particles may have different toxicological properties compared to larger particles. We evaluated the effect of ultrafine silica nanoparticles on mouse bone marrow-derived dendritic cells (BMDC) and murine dendritic cell line, DC2.4. The exposure of dendritic cells (DCs) to ultrafine silica nanoparticles showed a decrease in cell viability and an induction of cell death in size- and concentration-dependent manners. In addition, in order to examine the phenotypic changes of DCs following co-culture with silica nanoparticles, we added each sized-silica nanoparticle along with GM-CSF and IL-4 during and after DC differentiation. Expression of CD11c, a typical DC marker, and multiple surface molecules such as CD54, CD80, CD86, MHC class II, was changed by silica nanoparticles in a size-dependent manner. We also found that silica nanoparticles affect inflammatory response in DCs in vitro and in vivo. Finally, we found that p38 and NF-${\kappa}B$ activation may be critical for the inflammatory response by silica nanoparticles. Our data demonstrate that ultrafine silica nanoparticles have cytotoxic effects on dendritic cells and immune modulation effects in vitro and in vivo.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.611-618
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• 2023

Rhizome of Alisma orientale has been used as a traditional medicine for treating kidney diseases in East Asian countries. Its inhibitory effects on hypersensitivity responses have been reported for methanol extracts, with alisol B 23-acetate (AB23Ac) being the most active constituent among six terpenes in inhibiting the direct passive Arthus reaction. However, whether AB23Ac has efficacy against allergic asthma has not been tested to date. The in vivo efficacy of AB23Ac in an ovalbumin (OVA)-induced allergic asthma mouse model was evaluated by administrating AB23Ac before OVA sensitization or OVA challenge in BALB/c mice. AB23Ac suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of AB23Ac both before OVA sensitization and OVA challenge greatly lowered pulmonary resistance and the increase in immune cell counts and inflammatory responses around the peribronchial and perivascular regions. In addition, the inflammatory cytokine levels of Th1/Th2/Th17 cells in the bronchoalveolar lavage fluid decreased in the AB23Ac-treated groups. AB23Ac reduced the number of PAS-stained cells in the lungs. Furthermore, a computer modeling study indicated that AB23Ac can bind tightly to spleen tyrosine kinase (Syk). These results suggest that AB23Ac may ameliorate allergic asthma by suppressing immune responses in dendritic cells during sensitization and in mast cells during challenge periods.

• The Korea Journal of Herbology
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• v.34 no.2
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• pp.41-47
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• 2019

Objectives : A traditional herbal prescription, Kyung-Ok-Ko (KOK), has long been used in oriental medicine as an invigorant for age-related diseases, such as amnesia and stroke. However, the beneficial value of KOK for immune responses is largely unknown. Based on the above mentioned effects of KOK, other previous reports, and its use in traditional medicine, we hypothesized that KOK displays beneficial effects against methotrexate (MTX)-induced immune suppression. Methods : We investigated the effects of KOK (0.6 g/kg/day, oral (p.o.)) on deteriorated immunity caused by MTX (2 mg/kg/day, p.o.) in an immune suppression mouse model. MTX was fed to mice once a day for 7 days. After the immune responses of the mice deteriorated by MTX treatment, KOK in water was fed to the mice once a day for 14 days. We then measured the expression levels of various cytokines, such as T helper cell (Th1, Th2) cytokines, and the number of immune cells, such as spleen T cells, B cells, and macrophages. Results : The data showed that MTX decreased Th1 profiles (interferon $(IFN)-{\gamma}$, interleukin (IL)-2, IL-12) and the number of immune cells, and increased Th2 profiles (IL-4, IL-5, IL-13), which were normalized significantly by post-administration of KOK. However, there was no significant difference in body-weight gain between MTX- and KOK-treated mice. Conclusion : These results indicate that KOK has immune-enhancing functions and reduces immunotoxicity of MTX, suggesting that supplementation with KOK will improve immune responses clinically and be useful for the prevention of immune-related diseases.