• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2020년도 춘계학술대회
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• pp.86-86
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• 2020

The leaves of Staphylea bumalda (S. bumalda) as a deciduous tree distributed in Korea, China and Japan are used to treat respiratory diseases or inflammation. However, there is no scientific research on the immune-enhancing activity of S. bumalda leaves. Thus, in this study, we investigated the effect of water extracts from S. bumalda leaves (SBL) on the macrophage activity using mouse macrophage cells, RAW264.7. SBL increased production of immunomodulators such as NO, iNOS, IL-1β, IL-6, TNF-α and MCP-1 in RAW264.7 cells and activated phagocytic activity of RAW264.7 cells. Inhibition of TLR2 and TLR4 blocked SBL-mediated production of immunomodulators in RAW264.7 cells. In addition, SBL-mediated production of immunomodulators was attenuated by JNK inhibition in RAW264.7 cells. SBL increased JNK phosphorylation, while Inhibition of TLR2 and TLR4 blocked SBL-mediated JNK phosphorylation in RAW264.7 cells. These results are thought to be evidence that SBL activates JNK through stimulation of TLR2 and TLR4 in macrophage to induce the production of immunomodulators. In LPS-stimulated RAW264.7 cells, SBL inhibited over-production of immunomodulators. Summarizing the results, SBL showed immunostimulatory activity under normal conditions and immunosuppressive activity under LPS-induced excessive immune response conditions.

• 대한의생명과학회지
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• 제29권3호
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• pp.178-183
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• 2023

Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. Regulation of the cytotoxic activity of NK cells relies on integrated interactions between inhibitory receptors and numerous activating receptors that act in tandem to eliminate tumor cells efficiently. Conventional chemotherapy is designed to produce an anti-proliferative or cytotoxic effect on early tumor cell division. Therapies designed to kill cancer cells and simultaneously maintain host anti-tumor immunity are attractive strategies for controlling tumor growth. Depending on the drug and dose used, several chemotherapeutic agents cause DNA damage and cancer cell death through apoptosis, immunogenic cell death, or other forms of non-killing (i.e., mitotic catastrophe, senescence, autophagy). Among stress-induced immunostimulatory proteins, changes in the expression levels of NK cell activating and inhibitory ligands and tumor cell death receptors play an important role in the detection and elimination by innate immune effectors including NK cells. Therefore, we will address how these cytotoxic lymphocytes sense and respond to high and low concentrations of drug-induced stress to the drug cisplatin, among the various types of drugs that contribute to their anticancer activity.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2599-2605
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• 2013

The study aimed to evaluate immune-stimulating effects of a well-known Thai folkloric remedy when used for adjuvant therapy with conventional chemotherapeutics for treatment of breast cancer. Immunostimulating influence of the remedy (215 mg/kg body weight per day) on NK cell activity and TNF-${\alpha}$ release from the monocytes/macrophages were investigated in a total of 15 healthy women and 13 female patients with breast cancer (Group 1). The effect of breast tumor surgery on NK cell activity was further investigated in 18 female patients with breast cancer (Group 2). NK cell cytotoxic activity was determined by chromium release cytotoxic assay using K562, an erythroleukemic cell line. TNF-${\alpha}$ release from monocytes/macrophages separated from blood samples was determined through a biological assay using actinomycin D-treated L929 mouse fibroblast cells in the presence and absence of LPS. Baseline NK cell activity of the monocytes/macrophages separated from Group 2 patients expressed as %cytotoxicity was significantly lower than in the healthy subjects at E:T ratios of 100:1 and 25:1. In healthy subjects, there was no change in NK cell cytotoxic activity (%cytotoxicity or LU) following 1 and 2 weeks of treatment with the remedy compared with the baseline at various E:T ratios but the binding activity (%binding) was significantly increased after 2 weeks of treatment. The addition of one or two conventional chemotherapeutic regimens did not significantly reduce the NK cytotoxic activity but did affect release of TNF-${\alpha}$ in both unstimulated and LPS-stimulated samples. Surgery produced a significant suppressive effect on NK cell activity. The use of the remedy as an adjunct therapy may improve therapeutic efficacy and safety profiles of conventional chemotherapeutic regimens through stimulation of the immune system in cancer patients.

• 대한한방부인과학회지
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• 제27권2호
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• pp.46-58
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• 2014

Objectives: This study was designed to investigate intestinal immune system activation and anti-metastatic effect on cancer cells by orally administered extracts of Boyanghwano-tang. Methods: To observe immunomodulating effects of Boyanghwano-tang on Peyer's patch cells, we measured cytokines GM-CSF, IL-4. In addition to observing effects of Boyanghwano-tang on hematopoiesis, we measured proliferation of bone marrow cells mediated by Peyer's patch cells in vitro. IgA induction activated in intestinal content and serum was measured to observe the effect of orally administered Boyanghwano-tang on mucosal immune system. After administering ovalbumin (OVA) with Boyanghwano-tang, Proliferation of Peyer's patch cell was measured to investigate gut immunostimulatory effect. Anti-metastatic experiments were conducted in vivo mouse model by using colon 26-M3.1 carcinoma cell. Results: The amounts of GM-CSF and IL-4 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-regualted with Boyanghwano-tang. These results indicate that oral administration of Boyanghwano-tang 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 OVA with Boyanghwano-tang, IgA induction and Proliferation of peyer's patch cell was up-regulated with Boyanghwano-tang. These results means orally administered Boyanghwano-tang activates intestinal immune system and has an inhibitory effect on tumor metastasis. In addition, We found that orally administered Boyanghwano-tang significantly inhibited tumor metastasis in vivo. Conclusions: Orally administered Boyanghwano-tang appears to have considerable activity on the anti-metastasis by activation of immune system.

• 생약학회지
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• 제34권3호통권134호
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• pp.210-217
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• 2003

Korean mistletoe (Viscum album) extract has been found to posses immunostimulatory activity. In this study, Korean mistletoe extract, M11C (non-lectin components), was used to know whether this extract might activate mouse splenic macrophages to produce tumor necrosis $factor-{\alpha}\;(TNF-{\alpha}$) and might play a role in anticancer. To know the effect of M11C on the production of $TNF-{\alpha}$, the splenic macrophages were treated by the M11C, and then collected the supernatant (M11C stimulated splenic macrophage-conditioned media; MSCM). MSCM was analyzed for the $TNF-{\alpha}$ secretion by means of ELISA and immunoblotting, and mRNA expression was analyzed by RT-PCR. The S-180 murine sarcoma model was established to know the effect of M11C on the inhibition of tumor growth. M11C had the effect of $TNF-{\alpha}$ production from splenic macrophages performed by ELISA technique. This ELISA data was reconfirmed by immunoblotting assay. The effects of M11C on the expression of $TNF-{\alpha}$ mRNA from the macrophages was also shown. M11C also had the inhibitory effect of S-180 tumor growth. These data suggest that Korean mistletoe extract M11C may be used for an immunomodulator.

• 한국약용작물학회지
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• 제12권2호
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• pp.141-148
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• 2004

Two compounds from Gomisin N and Gomisin A were isolated from the fruits of Schizandra chinensis Baillon. The highest extraction yield as 21.36% was observed in the ethanol extract, compared to the yield obtained form the water extract. The extraction yields of the single compounds were measured to be 0.13 and 0.014 Gomisin A and Gomisin N, respectively. Approximately, 90% of the growth of human stomach adenocarcinoma cancer cells was inhibited after adding 1.0 g/l of the ethanol extract. The growth of the human normal lung cell was limited to 24% after adding the ethanol extract. The water extract lowered the specific secretion of $TNF-\acute{a}$ and IL-6 from T cells, $10.3{\times}10^{-4}\;pg/cell\;and\;12.1{\times}10^{-4}\;pg/cell$, respectively, compared to the ethanol extracts. On the other hand, a treatment with the ethanol extract increased the specific secretion of $TNF-\acute{a}$ and IL-6 from human T cells, to $11{\times}10^{-4}\;pg/cell\;and\;14.3{\times}10^{-4}\;pg/cell$, respectively. The crude ethanol extract had the highest effect on the differentiation of human promyelocytic leukemia cells compared to the other extracts and Gomisin A and N. In general, the biological activities of the extracts gradually decreased as the purification process proceeded, which suggests that higher immunostimulatory activities can be maintained by adding the crude extracts of the fruits rather than by adding a single compound.

• BMB Reports
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• 제40권4호
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• pp.486-493
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• 2007

Atopic dermatitis (AD) is a chronic inflammatory skin disease and the pathogenesis of AD is associated with the release of various cytokines/chemokines due to activated $Th_2$ immune responses. Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG dinucleotide in the context of particular base sequence (CpG motifs) are known to have the immunostimulatory activities in mice and to convert from Th2 to Th1 immune responses in AD. We aimed to investigate that CpG ODN, especially phosphodiester form, can stimulate the protective immunity in NC/Nga mice with AD. We isolated BMDCs from NC/Nga mice and then, cultured with GM-CSF and IL-4 for 6 days, and treated for 2 days by either phosphorothioate ODN or phosphodiester ODN. CpG ODN-treated DCs resulted in more production of IL-12. When CpG ODN-treated DCs were intravenously injected into the NC/Nga mice, the NC/Nga mice with CpG ODN-treated DCs showed significant improvement of AD symptoms and decrease of IgE level. Histopathologically, the NC/Nga mice skin with CpG ODN-treated DCs showed the decreased IL-4 and TARC expression comparing with non-injected mice. These results may suggest that phosphodiester CpG ODN-treated DCs might function as a potent adjuvant for AD in a mouse model.

• Journal of Microbiology and Biotechnology
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• 제28권2호
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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.

• Journal of Microbiology and Biotechnology
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• 제18권2호
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• pp.338-342
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• 2008

This study was performed to screen and select Lactobacillus strains from chicken feces for probiotic use in animals. Of these strains, strain AU had the highest immunostimulatory effect. Therefore, strain A12 was characterized as a potential probiotic. Strain A12 was tentatively identified as Lactobacillus acidophilus A12, using the API 50 CHL kit based on a 99.9% homology. L. acidophilus A12 was highly resistant to artificial gastric juice (pH 2.5) and bile acid (oxgall). Based on results from the API ZYM kit, leucine arylamidase, crystine arylamidase, acid phosphatase, naphthol-AS-BI-phosphohydrolase, ${\alpha}$-galactosidase, ${\beta}$-galactosidase, ${\alpha}$-glucosidase, ${\beta}$-glucosidase, and N-acetyl-${\beta}$-glucosamidase were produced by strain A12. L. acidophilus A12 showed resistance to several antibiotics (nisin, gentamicin, and erythromycin). The amount of interleukin $(IL)-1{\alpha}$ in $20{\times}$ concentrated supernatant from L. acidophilus A12 was approximately 156pg/ml. With regard to antioxidant activity, L. acidophilus A12 supernatant showed 60.6% DPPH radical scavenging activity. These results demonstrate the potential use of L. acidophilus A12 as health-promoting probiotics.

• IMMUNE NETWORK
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• 제12권6호
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• pp.296-300
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• 2012

Silica nanoparticles, which are applicable in many industrial fields, have been reported to induce cellular changes such as cytotoxicity in various cells and fibrosis in lungs. Because the immune system is the primary targeting organ reacting to internalized exogenous nanoparticles, we tried to figure out the immunostimulatory effect of silica nanoparticles in macrophages using differently sized silica nanoparticles. Using U937 cells we assessed cytotoxicity by CCK-8 assay, ROS generation by CM-$H_2DCFDA$, intracellular $Ca^{{+}{+}}$ levels by staining with Fluo4-AM and IL-8 production by ELISA. At non-toxic concentration, the intracellular $Ca^{{+}{+}}$ level has increased immediately after exposure to 15 nm particles, not to larger particles. ROS generation was detected significantly in response to 15 nm particles. However, all three different sizes of silica nanoparticles induced IL-8 production. 15 nm silica nanoparticles are more stimulatory than larger particles in cytotoxicity, intracellular $Ca^{{+}{+}}$ increase and ROS generation. But IL-8 production was induced to same levels with 50 or 100 nm particles. Therefore, IL-8 production induced by silica nanoparticles may be dependent on other mechanisms rather than intracellular $Ca^{{+}{+}}$ increase and ROS generation.