• IMMUNE NETWORK
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• v.5 no.4
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• pp.221-231
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• 2005

Background: Immune regulatory dendritic cells (DCs) play an important role in maintaining self-tolerance. Recent evidences demonstrate that DCs expressing indoleamine 2,3-dioxygenase (IDO), which is involved in tryptophan catabolism, play an important role in immunoregulation and tolerance and induce T cell apoptosis. This study was devised to examine the role of IDO in the oral tolerance induction in collagen-induced arthritis (CIA) mouse model. Methods: Beginning 2 weeks before immunization, CII was fed six times to DBA/1 mice and the effect on arthritis was assessed. In tolerized mice, $CD11c^+$ DCs were isolated and stimulated with CII, IFN-${\gamma}$, and LPS with or without IDO inhibitor, 1-methyl-DL-tryptophan (1-MT) and IDO expression by $CD11c^+$ DCs was analyzed using FACS and RT-PCR. The expression of IDO, MHC II, CD80, and CD86 by $CD11c^+$ DCs were examined using confocal microscopy. Regulatory effect of $CD11c^+$ DCs on Ag-specific T cell proliferative response to CII was examined by mixed lymphocyte reaction (MLR) with or without 1-MT. Results: The proportion of IDO-expressing $CD11c^+$ DCs was slightly higher in tolerized mice than in CIA mice and significantly increased after stimulation with CII, IFN-${\gamma}$, and LPS in an IDO-dependent manner. On confocal microscopic examination, the expression of IDO was higher and those of MHC II and CD86 were lower in CD11c + DCs from tolerized mice compared to those from CIA mice. On MLR, $CD11c^+$ DCs from tolerized mice inhibited T cell proliferative response to CII in an IDO-dependent manner. Conclusion: Enhanced IDO expression by $CD11c^+$ DCs from tolerized mice may contribute to the regulation of proliferative response of CII-reactive T cells and could be involved in the induction of oral tolerance to CII.

• Journal of Haehwa Medicine
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• v.19 no.2
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• pp.65-83
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• 2011

Various related factors and tissue changes in vitro and in vivo were observed to investigate the efficacy of HYBH on atopic dermatitis. The results are described below. HYBH improved the atopic dermatitis symptoms by naked eye examination, and significantly decreased dermatitis clinical index at 14 weeks. HYBH significantly decreased CD4+/CD45+, CD4+, CD8+, CD3+/CD69+ immune cell ratios in PBMC by 28%, 16%, 30%, 26% and 22% respectively. HYBH significantly decreased CD11b+/Gr-1+, CD3 immune cell ratios in dorsal skin by 35.3% and 67.5% respectively. HYBH significantly decreased the expression of IL-4 and IFN-${\gamma}$ in spleen by 23% and 15% respectively. HYBH significantly decreased the production rate of IL-5, IL-13 and histamine in serum by 17%, 23%, and 8.8% respectively and increased IL-17 production by 17%. HYBH significantly decreased immunoglubulins IgG1 and IgE production in serum. The results above indicated that treatment of HYBH improved atopic dermatitis symptoms by anti-oxidant activity and immune modulation activity as a clinical evidence. Also, different fermentation conditions using various microbial strains should be accumulated as the clinical evidence for broad application in the future.

• The Korean Journal of Food And Nutrition
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• v.19 no.2
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• pp.201-206
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• 2006

Numerous investigators have studied various activities of natural products and have found that they have not only nutritional effects, but also beneficial properties to cure various diseases and to maintain good health. Job's Tear(Yul-Moo) is a grass crop that has long been used in traditional medicine and as a nourishing food. Although its mechanism of action remains unclear, Job's Tear has been reported to exhibit anti-inflammatory, stomachic, anti-allergic, and anti-spastic effects and has been used in China for the treatment of warts, rheumatism, and neuralgia. Previous results in our laboratory demonstrated that the ethanol extract and the water extract of Job's Tear exerted an immune regulatory function on mice cells in vitro. The present study was performed to investigate the ex vivo effect of Job's Tear on immune function. Seven to eight weeks old mice(Balb/c) were fed chow diet ad libitum and water extract of Job's Tear was administered orally every other day for four weeks at two different concentrations(50 and 500mg/kg B.W.). Splenocytes proliferation with mitogen stimulation with Con A and LPS was enhanced at 50 mg/kg B.W. of Job's Tear compared to those of the control group. The results of this ex vivo study showed that proliferation of splenocytes and macrophage activation were seen in the mice orally administrated 50 mg/kg B.W. of Job's Tear water extracts. In conclusion, this study suggests that Job's Tear extracts may enhance immune function by regulating splenocyte proliferation and the cytokine prodution capacity of activated macrophages in mice.

• Journal of Microbiology and Biotechnology
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• v.29 no.5
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• pp.704-712
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• 2019

Although nanometric dead Lactobacillus plantarum has emerged as a potentially important modulator of immune responses, its underlying mechanism of action has not been fully understood. This study aimed to identify the detailed biochemical mechanism of immune modulation by micronized and heat-treated L. plantarum LM1004 (MHT-LM1004, <$1{\mu}m$ in size). MHT-LM1004 was prepared from L. plantarum LM1004 via culture in a specifically designed membrane bioreactor and heat treatment. MHT-LM1004 was shown to effectively induce the secretion of $TNF-{\alpha}$ and IL-6 and the mRNA expression of inducible nitric oxide synthase (iNOS). MHT-LM1004 enhanced the expression of TLR-2, phosphorylation of MAPKs (ERK), and nuclear translocation of $NF-{\kappa}B$ in a dose-dependent manner. Oral administration of MHT-LM1004 ($4{\times}10^9$ or $4{\times}10^{11}cells/kg$ mouse body weight) increased the splenocyte proliferation and serum cytokine levels. These results suggested that MHT-LM1004 effectively enhances early innate immunity by activating macrophages via the TLR-2/MAPK/$NF-{\kappa}B$ signalling pathway and that this pathway is one of the major routes in immune modulation by the Lactobacillus species.

• Korean Journal of Veterinary Research
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• v.54 no.2
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• pp.75-79
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• 2014

Bordetella (B.) bronchiseptica is a causative agent of swine atrophic rhinitis that promotes colonization of the mucous membrane of the swine nasal cavity by Pasteurella (P.) multocida. Mixed infection with B. bronchiseptica and P. multocida leads to growth inhibition of pigs, resulting in significant economic loss. There are many commercial vaccines for atrophic rhinitis, including B. bronchiseptica as a killed vaccine antigen (Ag). However, the immunogenicity of killed B. bronchiseptica Ag has not yet been elucidated; therefore, this study was conducted to investigate the immunogenicity of killed B. bronchiseptica Ag and the type of immune response it induces. In vitro assays using mouse spleen cells and flow cytometry revealed that B. bronchiseptica Ag induced high proliferation capability of lymphocytes, especially B lymphocytes, and the proliferating cells showed a significant response to interleukin (IL)-2. B. bronchiseptica Ag also enhanced the production of IL-12, a representative cytokine for cell-mediated immunity. In vivo experiments using mice showed that the injection of B. bronchiseptica Ag markedly induced Ag-specific antibody. Taken together, these results indicate that B. bronchiseptica Ag has high immunogenicity by itself.

• IMMUNE NETWORK
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• v.10 no.4
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• pp.126-134
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• 2010

Background: $CD8^+$ T cells contribute to the clearance of Hepatitis B virus (HBV) infection and an insufficient $CD8^+$ T cell response may be one of the major factors leading to chronic HBV infection. Since the HBx antigen of HBV can up-regulate cellular expression of several immunomodulatory molecules, we hypothesized that HBx expression in hepatocytes might affect $CD8^+$ T cell activity. Methods: We analyzed the activation and apoptosis of $CD8^+$ T cells co-cultured with primary hepatocytes rendered capable of expressing HBx by recombinant baculovirus infection. Results: Expression of HBx in hepatocytes induced low production of $interferon-{\gamma}$ and apoptosis of CD8+ T cells, with no effect on CD8 T cell proliferation. However, transcriptional levels of H-2K, ICAM-1 and PD-1 ligand did not correlate with HBx expression in hepatocytes. Conclusion: Our results suggest that HBx may inhibit $CD8^+$ T cell response by regulation of $interferon-{\gamma}$ production and apoptosis.

• Toxicological Research
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• v.24 no.3
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• pp.213-218
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• 2008

In this research, the genotoxic effects of Kong-Jin-Dan(KJD), a polyherbal formula were evaluated using the mouse micronucleus test. KJD was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2000, 1000 and 500 mg/kg. Cyclophosphamide was used as a known genotoxic agent in a positive control. The appearance of a micronucleus is used as an index for genotoxic potential. In addition, the changes on the total white blood cells and differential counts on the lymphocytes, neutrophils, eosinophils, basophils and monocytes in the prepared blood smears were also conducted to observe the possible immunosuppress. The results obtained indicated that KJD shows no genotoxicity effects up to 2000 mg/kg dosing levels, but KJD shows slight increased trends in the blood total leukocyte numbers as pharmacological effects of immune stimulation. In addition, it is also considered that there were no problems from cytotoxicity of KJD tested in this study because the polychromatic erythrocyte ratio was detected as > 0.42 in all tested groups.

• KSBB Journal
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• v.27 no.5
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• pp.295-300
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• 2012

Matured dendritic cells (DCs) begin migration with their release from the bone marrow (BM) into the blood and subsequent traffic into peripheral lymphoid and non-lymphoid tissues. Throughout this long movement, migrating DCs must apply specialized skills to reach their target destination. Non-invasive in vivo cell-tracking techniques are necessary to advance immune cell-based therapies. In this study, we used a DiD cell-tracking solution for in vivo dendritic cell tracking in naive mice. We tracked DiD (non-invasive fluorescence dye)-labeled mature dendritic cells using the Near Infrared (NIR) imaging system in normal mice. We examined the immunophenotype of DiD-labeled cells compared with non-labelled mature DCs, and obtained time-serial images of NIR-DC trafficking after mouse footpad injection. In conclusion, we confirmed that DiD-labeled DCs migrated into the popliteal lymph node 24 h after the footpad injection. Here, these data suggested that the cell tracking system with the stable fluorescence dye DiD was useful as a cell tracking tool to advance dendritic cell-based immunotherapy.

• BMB Reports
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• v.52 no.1
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• pp.47-55
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• 2019

Cellular senescence (CS) is one of hallmarks of aging and accumulation of senescent cells (SCs) with age contributes to tissue or organismal aging, as well as the pathophysiologies of diverse age-related diseases (ARDs). Genetic ablation of SCs in tissues lengthened health span and reduced the risk of age-related pathologies in a mouse model, suggesting a direct link between SCs, longevity, and ARDs. Therefore, senotherapeutics, medicines targeting SCs, might be an emerging strategy for the extension of health span, and prevention or treatment of ARDs. Senotherapeutics are classified as senolytics which kills SCs selectively; senomorphics which modulate functions and morphology of SCs to those of young cells, or delays the progression of young cells to SCs in tissues; and immune-system mediators of the clearance of SCs. Some senolytics and senomorphics have been proven to markedly prevent or treat ARDs in animal models. This review will present the current status of the development of senotherapeutics, in relation to aging itself and ARDs. Finally, future directions and opportunities for senotherapeutics use will discussed. This knowledge will provide information that can be used to develop novel senotherapeutics for health span and ARDs.

• Korean Journal of Plant Resources
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• v.34 no.4
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• pp.377-383
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• 2021

In this study, we investigated in vitro immunostimulatory activity of fruit extracts from Pyrus ussuriensis var. hakunensis (Nakai) T.B. Lee (PUF) using mouse macrophage RAW264.7 cells. PUF increased the production of immunostimulatory factors such as NO, iNOS, IL-1β, IL-6 and TNF-α, and phagocytic activity in RAW264.7 cells. The inhibition of TLR2 and TLR4 blocked PUF-mediated production of immunostimulatory factors in RAW264.7 cells. In addition, the inhibition of MAPKs signaling pathway reduced PUF-mediated production of immunostimulatory factors. From these results, PUF may have immunostimulatory activity via TLR2/4-mediated activation of MAPKs signaling pathway. Therefore, PUF expected to be used as a potential immune-enhancing agent.