• Journal of Life Science
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• v.24 no.10
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• pp.1151-1156
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• 2014

Traditional medicinal plants are widely used to treat many diseases, such as inflammation, infections, and even cancer. Ulmus macrocarpa Hance, a Chinese elm species, is distributed in Korea, China, and Japan. The stem bark is widely employed in Korean traditional medicine to treat dermatitis, mastitis, and edema. The aim of this study was to investigate whether water extract of U. macrocarpa Hance bark (Ulmus cortex) has a immune-modulating function in a mouse model. Three different concentrations (30 mg/kg, 100 mg/kg, and 300 mg/kg) of Ulmus cortex water extract (UCWE) were orally administered to mice for 14 days, and their immune responses were analyzed. Cytokines, such as interleukin (IL)-2, IL-12, and IFN-${\gamma}$, increased in the blood of UCWE-fed groups when compared with a control group. In contrast, the IL-4 level did not change in any of the UCWE-fed groups Cell-mediated cytotoxicity was also assayed using lymphokine-activated killer cells (LAK). LAK showed greater cytotoxicity in the UCWE-fed groups than LAK in the control group. Internal organ indices, such as liver, kidney, spleen, and thymus, were similar in all the groups, including the control group, indicating that UCWE may have been nontoxic in the experimental animals. These data suggest that UCWE has an immune-modulating function in a mouse model.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.2
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• pp.278-286
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• 2004

The objective of the current study was to determine the effects of arabinoxylane and PSP on mouse splenocytes, T cells, B cells and macrophages in vitro. Arabinoxylane and PSP directly induced the proliferation of spleen cells in a dose-dependent manner and increased IFN-${\gamma}$ synthesis. Especially, PSP induced IL-2, IL-4 and IL-10 production, Both arabinoxylane and PSP increased PFC (plaque forming cell) and RFC (rosette forming cell) formation. Arabinoxylane was not induced the proliferation of T cells, but PSP directly induced the proliferation of T cells in a high dose. Arabinoxylane and PSP increased the proliferation of B cells and the phagocytic effects of macrophage. When arabinoxylane and PSP were used in macrophage cell line stimulation, there was a marked induction of NO synthesis in a dose-dependent and an increased TNF-$\alpha$ and IL-6 synthesis. Especially, PSP also induced IL-1$\beta$ production. When arabinoxylane and PSP treated in macrophage cell line, there was induction of MHC class II expression. These results suggest that the capacity of arabinoxylane andPSP seem to act as a potent immunomodulator causing augmentation of immune cell activity, and with the absence of notable side-effects, arabinoxylane and PSP could be used as a biological response modifier having possible therapeutic effects against immunological disorders.

• IMMUNE NETWORK
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• v.12 no.6
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• pp.253-260
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• 2012

${\alpha}$-Mangostin is a xanthon derivative contained in the fruit hull of mangosteen (Garcinia mangostana L.), and the administration of ${\alpha}$-Mangostin inhibited the growth of transplanted colon cancer, Her/CT26 cells which expressed Her-2/neu as tumor antigen. Although ${\alpha}$-Mangostin was reported to have inhibitory activity against sarco/endoplasmic reticulum $Ca^{2+}$ ATPase like thapsigargin, it showed different activity for autophagy regulation. In the current study, we found that ${\alpha}$-Mangostin induced autophagy activation in mouse intestinal epithelial cells, as GFP-LC3 transgenic mice were orally administered with 20 mg/kg of ${\alpha}$-Mangostin daily for three days. However, the activation of autophagy by ${\alpha}$-Mangostin did not significantly increase OVA-specific T cell proliferation. As we assessed ER stress by using XBP-1 reporter system and phosphorylation of $eIF2{\alpha}$, thapsigargin-induced ER stress was significantly reduced by ${\alpha}$-Mangostin. However, coadministration of thapsigargin with ${\alpha}$-Mangostin completely blocked the antitumor activity of ${\alpha}$-Mangostin, suggesting ER stress with autophagy blockade accelerated tumor growth in mouse colon cancer model. Thus the antitumor activity of ${\alpha}$-Mangostin can be ascribable to the autophagy activation rather than ER stress induction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.3
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• pp.301-305
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• 2012

The purpose of this study is to investigate effects of Anisi stellati Fructus Water Extract on hydrogen peroxide production in RAW 264.7 mouse macrophages. Anisi stellati Fructus were extracted by hot water. Effects of Anisi stellati Fructus water extract (AS) on hydrogen peroxide production in RAW 264.7 were measured by dihydrorhodamine 123 assay after 20, 24, 28, 44, 48, and 52 h incubation at the concentrations of 10, 25, 50, and $100{\mu}g/mL$. For 20 h incubation, AS significantly increased hydrogen peroxide production in RAW 264.7 cells by $108.6{\pm}1.56%$, $109.5{\pm}1.94%$, $108.4{\pm}1.14%$, and $107.3{\pm}3.06%$ at the concentrations of 10, 25, 50, and $100{\mu}g/mL$ (P < 0.05) respectively. For 24, 28, 44, 48, and 52 h incubation, AS also significantly increased hydrogen peroxide production in RAW 264.7 cells at the concentrations of 10, 25, 50, and $100{\mu}g/mL$ (P < 0.05). These results suggest that Anisi stellati Fructus has the immune - enhancing property related with its increase of hydrogen peroxide production in macrophages.

• The Journal of the Korean Society for Microbiology
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• v.22 no.4
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• pp.377-392
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• 1987

Monoclonal antibody to the Escherichia coli heat-stable enterotoxin(ST) was produced to develop a rapid and convenient diagnostic method to the ST. The toxin was purified from culture supernatant of enterotoxigenic E. coli O148H28($ST^+/LT^+$) and conjugated to bovine serum albumin(BSA). The ST-BSA conjugate was used to immunize BALB/c mice and the immune spleen cells from these mice were fused with $P3{\times}63$ Ag8.V653 plasmacytoma cells. Hybridomas were screened by ELISA and positive hybridomas were cloned by limiting dilution. Finally, one stable clone (AS36) specific to ST was selected for further growth and characterization. Antibody titers of culture supernatant and ascitic fluid from BALB/c mice were 1:1,024 and 1:20,480 respectively in ELISA. The isotype and subclass of monoclonal antibody was IgG1 in sandwich ELISA. To test the neutralizing effect of monoclonal antibody on toxin activity of ST, mixture of ascitic fluid and ST was assayed by infant mouse assay and this monoclonel antibody was proved to be a neutralizing antibody. The titer of ascitic fluid which completely neutralized biological activity of 4 units of ST was 1:4. Purified ST was quantitatively measured by competitive ELISA and minimum amount of ST detectable by this assay was 250pg, which was an amount six-fold smaller than that detectable by infant mouse assay. Four reference strains of enterotoxigenic E. coli from WHO were detected by competitive ELISA and highly specific, sensitive and reproducible result was obtained.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.11 no.1
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• pp.1-22
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• 1998

During the last few years, nitric oxide(NO) as a potent macrophage-derived effector molecule against a variety of bacteria, parasites, and tumors has received increasing attention. More recent studies suggest that NO also has antiviral effects in both murine and human cells. The objective of the current study was to determine the effect of Yongdamsagantang(YST) on the production of NO. Stimulation of mouse peritoneal macrophages with YST after the treatment of recombinant $interferon-{\gammer}(rlFN-{\gammer})$ resulted in the increased NO synthesis. YST had no effect on NO synthesis by itself. When YST was used in combination with $rIFN-{\gammer}$, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of YST on NO synthesis was shown 6 hour after treatment with $rIFN-{\gammer}$. This increase in NO synthesis was reflected as increased amount of inducible NO synthase(iNOS) protein. NO production was inhibited by $N^G-monomethyl-L-arginine$. The increased production of NO from $rIFN-{\gammer}$ plus YST-stimulated cells was decreased by the treatment with staurosporin. In addition, synergy between $rIFN-{\gammer}$ and YST was mainly dependent on YST-induced tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ secretion. These results suggest that the capacity of YST to increase NO production from $rIFN-{\alpha}-primed$ mouse peritoneal macrophages is the result of YST-induced $TNF-{\alpha}$ secretion.

• Molecules and Cells
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• v.42 no.2
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• pp.151-160
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• 2019

Ultraviolet (UV) radiation of the sunlight, especially UVA and UVB, is the primary environmental cause of skin damage, including topical inflammation, premature skin aging, and skin cancer. Previous reports show that activation of nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) in human skin fibroblasts and keratinocytes after UV exposure induces the expression and release of proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), and subsequently leads to the production of matrix metalloproteases (MMPs) and growth factor basic fibroblast growth factor (bFGF). Here, we demonstrated that TNFR2-SKEE and TNFR2-SKE, oligopeptides from TNF receptor-associated factor 2 (TRAF2)-binding site of TNF receptor 2 (TNFR2), strongly inhibited the interaction of TNFR1 as well as TNFR2 with TRAF2. In particular, TNFR2-SKE suppressed UVB- or $TNF-{\alpha}$-induced nuclear translocalization of activated $NF-{\kappa}B$ in mouse fibroblasts. It decreased the expression of bFGF, MMPs, and COX2, which were upregulated by $TNF-{\alpha}$, and increased procollagen production, which was reduced by $TNF-{\alpha}$. Furthermore, TNFR2-SKE inhibited the UVB-induced proliferation of keratinocytes and melanocytes in the mouse skin and the infiltration of immune cells into inflamed tissues. These results suggest that TNFR2-SKE may possess the clinical potency to alleviate UV-induced photoaging in human skin.

• Journal of Pharmacopuncture
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• v.12 no.4
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• pp.89-96
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• 2009

Objectives : The purpose of this study is to investigate the effect of Water Extract from Lactobacillus pentosus-fermented ARTEMISIAE ARGI FOLIUM (AFL) on nitric oxide production of mouse macrophage Raw 264.7 cells impaired by various toxicants such as gallic acid, EtOH, nicotine, acetaminophen, and acetaldehyde. Methods : ARTEMISIAE ARGI FOLIUM was fermented with Lactobacillus pentosus and extracted by water. Nitric oxide production of mouse macrophage Raw 264.7 cells was measured by Griess reagent assay. Examined concentrations of AFL were 10, 50, 100, 200, 400 ug/mL. Results : The results of the experiment are as below. 1. AFL at the concentration of 400 ug/mL significantly recovered nitric oxide production which was reduced by gallic acid (100 uM) in Raw 264.7 cells. 2. AFL at the concentration of 200, 400 ug/mL significantly recovered nitric oxide production which was reduced by EtOH (100 uM) in Raw 264.7 cells. 3. AFL at the concentration of 400 ug/mL significantly recovered nitric oxide production which was reduced by nicotine (1mM) in Raw 264.7 cells. 4. AFL at the concentration of 200, 400 ug/mL significantly recovered nitric oxide production which was reduced by acetaminophen(2 mM) in Raw 264.7 cells. 5. AFL at the concentration of 200, 400 ug/mL significantly recovered nitric oxide production which was reduced by acetaldehyde (200 uM) in Raw 264.7 cells. Conclusions : AFL could be supposed to have the immune-enhancing activity related with nitric oxide production of macrophage impaired by various toxicants.

• Journal of Environmental Health Sciences
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• v.49 no.1
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• pp.22-29
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• 2023

Background: The existing research results on the combined toxicity of these pollutants using mammals, such as rodents, are insufficient, especially in relation to changes in the immune system. Objectives: This study aims at evaluating the cellular immune response to PE-MPs solely or when combined with Pb, which possess excellent adsorption capacity with PE-MPs and is commonly co-exposed in our daily lives. Methods: The study investigated the cellular immune function of 9-week ICR mice with 28 days exposure to PE-MPs (2 mg/mouse/day) and Pb (0.1 mM in distilled water) individually and in combination. PE-MPs were administered via gastric intubation while the lead intake was conducted via the oral drinking water route. Cellular immunity was evaluated by analyzing the production for T_H1 cytokines namely, TNF-α and IFN-𝛾 and T_H2 cytokines, IL-4 and IL-6 in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo. Results: Both the PE-MPs only and the PE-MPs+Pb exposure group revealed an increased T_H1 response with elevated TNF-α and IFN-𝛾 levels and downregulated T_H2 response with low IL-4, and IL-6 production levels compared to the control group. Furthermore, an increased IFN-𝛾/IL-4 ratio was found in the PE-MPs only and PE-MPs+Pb exposure groups, which indicated the skewedness to T_H1 response. Meanwhile, reduced blood hemoglobin levels and increased levels of IL-4, the dominant T_H2 cytokine in the Pb-only exposure group, were observed. Conclusions: Our current findings on the predominance of T_H1 immune response in the PE-MPs and PE-MPs+Pb groups suggest that PE-MPs could be responsible for the predominant induction of the cellular immune changes. This finding could be used as an important landmark in research related to T_H1 predominance, such as autoimmune diseases. It suggests that additional research on immune modulation using longer exposure durations or the same exposure route is required to elucidate stronger findings.

• IMMUNE NETWORK
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• v.21 no.4
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• pp.30.1-30.12
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• 2021

High expression of mitofusin-2 (MFN2), a mitochondrial fusion protein, has been frequently associated with poor prognosis of patients with cervical cancer. Here, we aimed to identify the function of MFN2 in cervical cancer to understand its influence on disease prognosis. To this end, from cervical adenocarcinoma, we performed an MTT assay and quantitative RT-PCR (qRT-PCR) analysis to assess the effects of MFN2 on the proliferation and of HeLa cells. Then, colony-formation ability and tumorigenesis were evaluated using a tumor xenograft mouse model. The migration ability related to MFN2 was also measured using a wound healing assay. Consequently, epithelial-mesenchymal transition (EMT) of MFN2-knockdowned HeLa cells originating from adenocarcinoma. markers related to MFN2 were assessed by qRT-PCR. Clinical data were analyzed using cBioPortal and The Cancer Genome Atlas. We found that MFN2 knockdown reduced the proliferation, colony formation ability, migration, and in vivo tumorigenesis of HeLa cells. Primarily, migration of MFN2-knockdowned HeLa cells decreased through the suppression of EMT. Thus, we concluded that MFN2 facilitates cancer progression and in vivo tumorigenesis in HeLa cells. These findings suggest that MFN2 could be a novel target to regulate the EMT program and tumorigenic potential in HeLa cells and might serve as a therapeutic target for cervical cancer. Taken together, this study is expected to contribute to the treatment of patients with cervical cancer.