• Journal of Ginseng Research
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• v.40 no.1
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• pp.18-27
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• 2016

Background: It is not clear whether ginseng affects cyclosporine A (CsA)-induced desirable immunosuppressive action. In this study, we evaluated the immunological influence of combined treatment of ginseng with CsA. Methods: Using CD4+ T cells from mouse spleens stimulated with the T cell receptor (TCR) or allogeneic antigen-presenting cells (APCs), we examined the differentiation of naïve T cells into T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and their cytokine production during treatment by Korean Red Ginseng extract (KRGE) and/or CsA. The influence of KRGE on the allogeneic T cell response was evaluated by mixed lymphocyte reaction (MLR). We also evaluated whether signal transducer and activator of transcription 3 (STAT3) and STAT5 are implicated in this regulation. Results: Under TCR stimulation, KRGE treatment did not affect the population of CD4+interferon gamma ($IFN{\gamma}$)+ and CD4+interleukin (IL)-4+ cells and their cytokine production compared with CsA alone. Under the Th17-polarizing condition, KRGE significantly reduced the number of CD4+IL-17+ cells and CD4+/phosphorylated STAT3 (p-STAT3)+ cells, but increased the number of CD4+CD25+forkhead box P3 (Foxp3)+ cells and CD4+/p-STAT5+ cells compared with CsA alone. In allogeneic APCs-stimulated CD4+ T cells, KRGE significantly decreased total allogeneic T cell proliferation. Consistent with the effects of TCR stimulation, KRGE reduced the number of CD4+IL-17+ cells and increased the number of CD4+CD25+Foxp3+ cells under the Th17-polarizing condition. Conclusion: KRGE has immunological benefits through the reciprocal regulation of Th17 and Treg cells during CsA-induced immunosuppression.

• Journal of Acupuncture Research
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• v.22 no.3
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• pp.23-35
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• 2005

Objective : The aim of the study is to investigate the effect of electro-acupuncture (EA) on ST36 to modulate immune reaction in BALB/c mice immunized intraperitoneally with 2,4-dinitrophenylated keyhole limpet protein(DNP-KLH). Methods : Experimental mice were divided into four groups : 1) Normal group was not performed by any operation. 2) IM(Immunized) group was immunized intraperitoneally with DNP-KLH and aluminum hydroxide without electro-acupunture stimulation. 3) IM-EA(immunized-elctro- acupuncture) group was performed by successive electro-acupuncture on the ST36 acupoint after immunization. 4) IM-NA(immunized-naloxone) group was performed by immunization and electro-acupuncture with same method, but naloxone was injected intraperitoneally 30 minutes before eletro-acupuncture to inhibit the opiate receptor in spleen. Serum total immunoglobulin I(IgE) and antigen-specific IgE was measured in each group. The expression of interferon-${\gamma}$ and interleukin-4 mRNA in spleen was researched by real-time RT-PCR Results : Serum total-IgE and antigen-specific IgE were significantly decreased only in IM-EA group. The expression of interleukin-4 in spleen cell was significantly reduced not only in IM-EA group, but also in IM-EA group. Conclusions : Above results indicate that the mechanism of immunomodulatory effect of electro-acupuncture is related to opioid system especially in B-cell immune reaction. Further research on the T-cell immunity is necessary to explain the mechanism of immunomodulatory effect of electro-acupuncture.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.29 no.3
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• pp.289-297
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• 2019

Objectives: To identify the positive rate of and the risk factors associated with latent tuberculosis infection(LTBI) in mine workers, the objectives of the present study evaluated those among former mine workers. Methods: Between January 2015 and May 2017, former male mine workers who had been subjects for epidemiology research for work-related chronic obstructive pulmonary disease(COPD) and had received QuantiFERON-$TB^{(R)}$ Gold In-Tube(QFT-GIT) from the Institute of Occupation and Environment(IOE) under Korea Workers' Compensation and Welfare Service(KCOMWEL) were selected as the study subjects. To identify significant variables for increased risk of LTBI, logistic regression analysis was performed. Results: A total of 736 male former mine workers were selected as study subjects. The positive rate of LTBI among subjects was 69.2%(509/736). The current smoking[odds ratio(OR), 2.3; 95% confidence interval(CI), 1.1-4.9], COPD(OR, 1.4; 95% CI, 0.9-2.3), department loading(OR, 1.8; 95% CI, 0.9-3.4) and mining(OR, 1.5; 95% CI, 0.9-2.5), and working duration of over 20(OR, 1.6; 95% CI, 0.9-3.1) and over 30 years(OR, 2.2; 95% CI, 0.9-4.9) were associated with increased risk of LTBI. The interferon-gamma(IFN-${\gamma}$) level after stimulation with Mycobacterium tuberculosis(MTB)-specific antigens showed a significantly negative correlation with age(r=-0.126). Conclusions: The present study determined that the high positive rate of LTBI among mine workers was associated with not only the host factors but also the occupational exposure to mine dust.

• Journal of Ginseng Research
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• v.39 no.1
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• pp.29-37
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• 2015

Background: Panax ginseng (i.e., ginseng) root is extensively used in traditional oriental medicine. It is a modern pharmaceutical reagent for preventing various human diseases such as cancer. Ginsenosidesd-the major active components of ginsengd-exhibit immunomodulatory effects. However, the mechanism and function underlying such effects are not fully elucidated, especially in human monocytes and dendritic cells (DCs). Methods: We investigated the immunomodulatory effect of ginsenosides from Panax ginseng root on $CD14^+$ monocytes purified from human adult peripheral blood mononuclear cells (PBMCs) and on their differentiation into DCs that affect $CD4^+$ T cell activity. Results: After treatment with ginsenoside fractions, monocyte levels of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 increased through phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK). After treatment with ginsenoside fractions, TNF-${\alpha}$ production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes.We confirmed that DCs derived from $CD14^+$ monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the costimulatory molecules CD80 and CD86. The expression of these costimulatory molecules decreased in LPS-treated DCs exposed to ginsenoside fractions, compared to their expression in LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, LPS-treated Gin-DCs could not induce proliferation and interferon gamma (IFN-${\gamma}$) production by $CD4^+$ T cells with the coculture of Gin-DCs with $CD4^+$ T cells. Conclusion: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of LPS-treated DCs and downregulate $CD4^+$ T cells.

• Journal of Animal Science and Technology
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• v.64 no.1
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• pp.166-182
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• 2022

Deer antler velvet is widely used in traditional medicine for its anti-aging, antioxidant, and immunity-enhancing effects. However, few studies have reported on the discovery of probiotic strains for deer antler fermentation to increase functional ingredient absorption. This study evaluated the ability of probiotic lactic acid bacteria to enhance the concentrations of bioactive molecules (e.g., sialic acid and gamma-aminobutyric acid [GABA]) in extracts of deer antler velvet. Seventeen strains of Lactobacillus spp. that were isolated from kimchi and infant feces, including L. sakei, L. rhamnosus, L. brevis, and L. plantarum, and those that improved the life span of Caenorhabditis elegans were selected for evaluation. Of the 17 strains, 2 (L. rhamnosus LFR20-004 and L. sakei LFR20-007) were selected based on data showing that these strains increased both the sialic acid and GABA contents of deer antler extract after fermentation for 2 d and significantly improved the life span of C. elegans. Co-fermentation with both strains further increased the concentrations of sialic acid, GABA, and metabolites such as short-chain fatty acids and amino acids. We evaluated the biological effects of the fermented antler velvet (FAV) on the antibacterial immune response in C. elegans by assessing worm survival after pathogen infection. The survival of the C. elegans conditioned with FAV for 24h was significantly higher compared with that of the control worm group fed only normal feed (non-pathogenic E. coli OP50) exposed to E. coli O157:H7, Salmonella typhi, and Listeria monocytogenes. To evaluate the protective effects of FAV on immune response, cyclophosphamide (Cy), an immune-suppressing agent was treated to in vitro and in vivo. We found that FAV significantly restored viability of mice splenocytes and immune promoting-related cytokines (interleukin [IL]-6, IL-10, inducible nitric oxide synthase [iNOS], interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) were activated compared to non-fermented deer antlers. This finding indicated the protective effect of FAV against Cy-induced cell death and immunosuppressed mice. Taken together, our study suggests that immune-promoting antler velvet can be produced through fermentation using L. rhamnosus LFR20-004 and L. sakei LFR20-007.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.3
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• pp.269-278
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• 2016

In searching for novel agents for skin anti-aging from natural resources, we found that the extract of the fruiting bodies of Ramaria formosa (R. formosa) had significant antioxidant and human neutrophil elastase (HNE) inhibitory activities. R. formosa extract exhibited a considerable DPPH radical scavenging activity with an antioxidant content of 117.0mg/mL (ascorbic acid equivalents) at the concentration of $500{\mu}g/mL$. The capacity of R. formosa extract to scavenge peroxy radicals measured by ORAC assay also showed dose-dependent antioxidant effect with $ORAC_{Roo}$ (trolox equivalents, $1{\mu}M$) values of 0.8, 5.2, and 7.8 at the concentrations of 1, 10, and $20{\mu}g/mL$. The cellular antioxidant capacity of R. formosa extract was investigated by assaying the cellular fluorescence intensity using dichlorodihydrofluorescein (DCF). The cellular oxidative stress induced by AAPH, $Cu^{2+}$ or $H_2O_2$ in HepG2 cells was significantly attenuated by more than 30% at $20{\mu}g/mL$ of R. formosa extract. HNE activity was reduced by treatment with R. formosa extract in a dose-dependent manner, and the $ED_{50}$ value for the ethanol extract of R. formosa was $42.9{\mu}g/mL$. R. formosa extract did not exhibited antimicrobial activity against four microorganisms including Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), Candida albicans (C. albicans), Aspergillus oryzae (A. oryzae). Furthermore, the extract did not affect the inflammatory cytokine production of interleukin-10 and interferon-${\gamma}$ in NK92 cells. From the above results, we found that R. formosa extract has considerable antioxidant and elastase inhibitory effects, and does not stimulate immune cells. These findings suggest that R. formosa extract may be used as a bioactive component in cosmetic composition.

• Journal of Periodontal and Implant Science
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• v.24 no.2
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• pp.321-339
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• 1994

The cytokines released by osteoblasts induce bone resorption via the differentiation of osteoclast precursors. In this process, $interleukin-1{\beta}$($IL-1{\beta}$)-induced bone resorption is mediated by granulocyte macrophage-colony stimulation factor(GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor ${\alpha}$($TNF-{\alpha}$) released from osteoblasts. Since these cytokines (GM-CSF, IL-6, $TNF-{\alpha}$) are produced by not only osteoblasts but also monocytes, and interleukin-10(I1-10) inhibits the secretion of these cytokines from monocytes, it may be speculated that IL 10 could modulate the production of GM-CSF, IL-6, and $TNF-{\alpha}$ by osteoblasts, then control $IL-1{\beta}-induced$ bone resorption. Therefore, the aims of the present study were to examine the effects of IL-10 on bone resorption. The sixten or seventeen-day pregnant ICR mice were injected with $^{45}Ca$ and sacrificed one day after injection. Then fetal mouse calvaria prelabeled with $^{45}Ca$ were dissected out. In order to confirm the degree of bone resorption, mouse calvaria were treated with Lipopolysaccharide(LPS), $TNF-{\alpha}$, $IL-1{\alpha}$, IL-8, $IL-1{\beta}$, and $IL-1{\alpha}$, Then, IL-10 and $interferon-{\gamma}$ ($IFN-{\gamma}$) were added to calvarial medium, in an attempt to evaluate the effect of $IL-1{\beta}-induced$ bone resorption. In addition, osteoclasts formation in bone marrow cell cultures, and the concentration of IL-6, $TNF-{\alpha}$, and GM-CSF produced from mouse calvarial cells were investigated in response to $IL-1{\beta}$ alone and simultaneously adding f $IL-1{\beta}$ and IL-10. The degree of bone resorption was expressed as the ratio of $^{45}Ca$ release(the treated/the control). The osteoclasts in bone marrow cultures were indentified by tartrate resistant acid phosphatase(TRAP) stain and the concentration of the cytokines was quantified using enzyme linked immunosorbent method. As results of these studies, bone resorption was induced by LPS(1 ng/ml ; the ratio of $^{45}Ca$ release, $1.14{\pm}0.07$). Also $IL-1{\beta}$(1 ng/ml), $IL-1{\alpha}$(1 ng/ml), and $TNF-{\alpha}$(1 ng/ml) resulted in bone resorption(the rations of $^{45}Ca$ release, $1.61{\pm}0.26$, $1.77{\pm}0.03$, $1.20{\pm}0.15$ respectively), but IL-8 did not(the ratio of $^{45}Ca$ release, $0.93{\pm}0.21$). The ratios of $^{45}Ca$ release in response to IL-10(400 ng/ml) and $IFN-{\gamma}$(100 ng/ml) were $1.24{\pm}0.12$ and $1.08{\pm}0.04$ respectively, hence these cytokines inhibited $IL-1{\beta}$(1 ng/ml)-induced bone resorption(the ratio of $^{45}Ca$ release $1.65{\pm}0.24$). While $IL-1{\beta}$(1 ng/ml) increased the number of TRAP positive multinulcleated cells in bone marrow cultures($20{\pm}11$), simultaneously adding $IL-1{\beta}$(1 ng/ml) and IL-10(400 ng/ml) decreased the number of these cells($2{\pm}2$). Nevertheless, IL-10(400 ng/ml) did not affect the IL-6, GM-CSF, and $TNF-{\alpha}$ secretion from $IL-1{\beta}$(1 ng/ml)-activated mouse calvarial cells. From the above results, it may be suggested that IL-10 inhibites $IL-1{\beta}-induced$ osteoclast differntiation and bone resorption. However, the inhibitory effect of IL-10 on the osteoclast formation seems to be mediated not by the reduction of IL-6, GM-CSF, and $TNF-{\alpha}$ production, but by other mechanisms.

• Korean Journal of Poultry Science
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• v.41 no.3
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• pp.205-215
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• 2014

The aim of this study was to determine the effects of stocking density and strain on the performance and physiological adaptive responses including the plasma corticosterone content and the level of mRNA expression of pro-inflammatory cytokines and antioxidant enzymes in broiler chicks. A total of 300 birds of two strains (150 Ross strain vs. 150 Cobb strain) aged 3-d old were allotted into two stocking densities (standard stocking density,$0.046m^2/bird$ vs. high stocking density, $0.023m^2/bird$) in battery cages by $2{\times}2$ factorial designs with ten replicates until 35 d of age. There was no significant strain effect on body weight, feed intakes and feed to gain ratio and the relative organ weights. However body weight, feed intakes and relative organ weight were found to be significantly (P<0.05) affected by the effect of stocking density. Plasma corticosterone level was not affected by both stocking density and strain effects. Hepatic mRNA expression of pro-inflammatory cytokines including interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, IL-18 and interferon-gamma (IFN-${\gamma}$) was not significantly changed by the effects of strain and stocking density. However, the mRNA expression of glutathione peroxidase (GPX) was affected by strain, showing that Ross strain decreased (P<0.05) the GPX expression. With respect to the effect of stocking density, there was a significant (P<0.05) increase in superoxide dismutase (SOD) and catalase (CAT) and GPX mRNA expression in the liver from high stocking density group. Splenic pro-inflammatory cytokine expression was not also affected by stocking density and strain, except that IL-18 mRNA significantly (P<0.05) decreased in Cobb strain under high stocking density. The mRNA expression of SOD and CAT was significantly (P<0.05) affected by the effects of stocking density and strain. In conclusion, growth performance was not affected by strain but stocking density. Although mRNA expression of major pro-inflammatory cytokines was not changed by stocking density and strain, antioxidant enzyme was significantly affected by stocking density, strain or even organ in birds under summer conditions. More detailed studies still needed to be explored to elucidate the effects of environmental conditions and genetic background on physiological responses in birds.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.182-195
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• 2001

Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$l_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$1_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.40.1-40.15
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• 2020

The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain. Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord. Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved. We explored whether GRIM-19 ameliorated MS by increasing the levels of inflammatory cytokines and immune cells; we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to this end. Six-to-eight-week-old male C57BL/6, IFNγ-knockout (KO), and GRIM-19 transgenic mice were used; EAE was induced in all strains. A GRIM-19 overexpression vector (GRIM19 OVN) was electrophoretically injected intravenously. The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM-19 OVN. GRIM19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance.