• IMMUNE NETWORK
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• v.5 no.1
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• pp.11-15
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• 2005

Background: Throughtout the last three decades, the therapy of leukemias and lymphoma has set the stage for curative cancer therapy in systemic malignant disease. This was the result of an integrated work of basic reaserch and clinical investigators leading to more aggressive albeit tolerable protocol of chemotherapy and radiotherapy. High dose therapy marks the most elaborated strategies in this field today. However, intensification of conventional therapeutic modalities as mentioned has to be based on new approaches and the exploration of new antineoplastic mechanisms. This insight has resulted in immune therapy of cancer. Among the cells of the immune system, natural killer (NK) cells and T cells are of major interest for the development of therapeutic strategies. Methods: Cytotoxicity to target cells was measured by LDH release method, Characterization of activated lymphocyte was measured by Flow cytometry analysis. Anti-CD3, 16, 56 monoclonal antibody and IL-2 were used for the activation of NK and T cell. The analysis of effect of activated lymphocyte, in vivo, were used by Balb/c nude mouse. Results and Conclusion: Cytotoxicity to K562 cells was significantly higher in the mixture group of NK and T cells than that of a group of activating T cells. The survivors and the rate of reduction of size of tumor craft of nude mouse group treatment with activated lymphocyte was higher than that of the group without treatment with activated lymphocyte. Therefore, this results are suggested that the activated lymphocytes by anti-CD3, CD16 and CD56 can reduce the malignancy effect of lymphoma.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.190-201
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• 2024

Background: Deposition of immune complexes drives podocyte injury acting in the initial phase of lupus nephritis (LN), a process mediated by B cell involvement. Accordingly, targeting B cell subsets represents a potential therapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possesses nephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulations remain elusive. Methods: Female MRL/lpr mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed by measurements of anti-dsDNA antibodies, inflammatory chemokines, and metabolite profiles on renal samples. Podocyte function and ultrastructure were detected. Publicly available single-cell RNA sequencing data and flow cytometry analysis were employed to investigate B cell subpopulations. Metabolomics analysis was adopted. SIRT1 and AMPK expression were analyzed by immunoblotting and immunofluorescence assays. Results: CK reduced proteinuria and protected podocyte ultrastructure in MRL/lpr mice by suppressing circulating anti-dsDNA antibodies and mitigating systemic inflammation. It activated B cell-specific SIRT1 and AMPK with Rhamnose accumulation, hindering the conversion of renal B cells into plasma cells. This cascade facilitated the resolution of local renal inflammation. CK facilitated the clearance of deposited immune complexes, thus reinstating podocyte morphology and mobility by normalizing the expression of nephrin and SYNPO. Conclusions: Our study reveals the synergistic interplay between SIRT1 and AMPK, orchestrating the restoration of renal B cell subsets. This process effectively mitigates immune complex deposition and preserves podocyte function. Accordingly, CK emerges as a promising therapeutic agent, potentially alleviating the hyperactivity of renal B cell subsets during LN.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.291-301
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• 2023

Introduction: Non-small cell lung cancer (NSCLC) patients are particularly vulnerable to the Coronavirus Disease-2019 (COVID-19). Currently, no anti-NSCLC/COVID-19 treatment options are available. As ginsenoside Rg3 is beneficial to NSCLC patients and has been identified as an entry inhibitor of the virus, this study aims to explore underlying pharmacological mechanisms of ginsenoside Rg3 for the treatment of NSCLC patients with COVID-19. Methods: Based on a large-scale data mining and systemic biological analysis, this study investigated target genes, biological processes, pharmacological mechanisms, and underlying immune implications of ginsenoside Rg3 for NSCLC patients with COVID-19. Results: An important gene set containing 26 target genes was built. Target genes with significant prognostic value were identified, including baculoviral IAP repeat containing 5 (BIRC5), carbonic anhydrase 9 (CA9), endothelin receptor type B (EDNRB), glucagon receptor (GCGR), interleukin 2 (IL2), peptidyl arginine deiminase 4 (PADI4), and solute carrier organic anion transporter family member 1B1 (SLCO1B1). The expression of target genes was significantly correlated with the infiltration level of macrophages, eosinophils, natural killer cells, and T lymphocytes. Ginsenoside Rg3 may benefit NSCLC patients with COVID-19 by regulating signaling pathways primarily involved in anti-inflammation, immunomodulation, cell cycle, cell fate, carcinogenesis, and hemodynamics. Conclusions: This study provided a comprehensive strategy for drug discovery in NSCLC and COVID-19 based on systemic biology approaches. Ginsenoside Rg3 may be a prospective drug for NSCLC patients with COVID-19. Future studies are needed to determine the value of ginsenoside Rg3 for NSCLC patients with COVID-19.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.4
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• pp.287-295
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• 2022

Staphylococcus aureus (S. aureus) is known to induce apoptosis of host immune cells and impair phagocytic clearance, thereby being pivotal in the pathogenesis of atopic dermatitis (AD). Adipose-derived stem cells (ASCs) exert therapeutic effects against inflammatory and immune diseases. In the present study, we investigated whether systemic administration of ASCs restores the phagocytic activity of peripheral blood mononuclear cells (PBMCs) and decolonizes cutaneous S. aureus under AD conditions. AD was induced by injecting capsaicin into neonatal rat pups. ASCs were extracted from the subcutaneous adipose tissues of naïve rats and administered to AD rats once a week for a month. Systemic administration of ASCs ameliorated AD-like symptoms, such as dermatitis scores, serum IgE, IFN-γ⁺/IL-4⁺ cell ratio, and skin colonization by S. aureus in AD rats. Increased FasL mRNA and annexin V⁺/7-AAD⁺ cells in the PBMCs obtained from AD rats were drastically reversed when co-cultured with ASCs. In contrast, both PBMCs and CD163⁺ cells bearing fluorescent zymosan particles significantly increased in AD rats treated with ASCs. Additionally, the administration of ASCs led to an increase in the mRNA levels of antimicrobial peptides, such as cathelicidin and β-defensin, in the skin of AD rats. Our results demonstrate that systemic administration of ASCs led to decolonization of S. aureus by attenuating apoptosis of immune cells in addition to restoring phagocytic activity. This contributes to the improvement of skin conditions in AD rats. Therefore, administration of ASCs may be helpful in the treatment of patients with intractable AD.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.96-102
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• 2003

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccines induce very potent systemic anti-tumor immunity in preclinical and clinical models. Our previous phase I clinical trial in patients with metastatic renal cell carcinoma (RCC) has demonstrated both immune cell infiltration at vaccine sites and T cell-mediated delayed-type hypersensitivity (DTH) response to whole tumor cell vaccines. Methods: To investigate the immune responses to autologous genetically- modified tumor cell vaccines, tumor-specific $CD8^+$ T cell lines were generated from peripheral blood lymphocytes (PBL) of a RCC patient 1.24 by repeated in vitro stimulation with either B7.1-transduced autologous RCC tumor cells or B7.1-transduced autologous tumor cells treated with interferon gamma ($IFN{\gamma}$), and cloned by limiting dilution. Results: Among several RCC-specific cytotoxic T lymphocytes (CTLs), a $CD4^+/CD8^+$ double positive T cell clone (17/A2) appeared to recognize $IFN{\gamma}$-treated autologous RCC restricted by HLA-B39. The 17/A2 also recognized other HLA-B39 positive RCC tumor cells after $IFN{\gamma}$ treatment. Conclusion: These results demonstrate that autologous RCC vaccination successfully generates the tumor-specific CTL 17/A2, and suggest that the presentation and recognition of the tumor antigen by the 17/A2 might be upregulated by $IFN{\gamma}$.

• Clinical and Experimental Pediatrics
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• v.58 no.7
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• pp.239-244
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• 2015

The complement system is part of the innate immune response and as such defends against invading pathogens, removes immune complexes and damaged self-cells, aids organ regeneration, confers neuroprotection, and engages with the adaptive immune response via T and B cells. Complement activation can either benefit or harm the host organism; thus, the complement system must maintain a balance between activation on foreign or modified self surfaces and inhibition on intact host cells. Complement regulators are essential for maintaining this balance and are classified as soluble regulators, such as factor H, and membrane-bound regulators. Defective complement regulators can damage the host cell and result in the accumulation of immunological debris. Moreover, defective regulators are associated with several autoimmune diseases such as atypical hemolytic uremic syndrome, dense deposit disease, age-related macular degeneration, and systemic lupus erythematosus. Therefore, understanding the molecular mechanisms by which the complement system is regulated is important for the development of novel therapies for complement-associated diseases.

• Journal of Microbiology and Biotechnology
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• v.15 no.4
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• pp.740-744
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• 2005

Bifidobacterium has been previously shown to potentiate immune function, which was mediated through the stimulation of cytokine production by macrophage. This study was performed to further characterize the effective component of Bifidobacterium by measuring the level of interleukin (IL)-6 cytokine using the RAW 264.7 murine cell line as a macrophage model. RAW 264.7 cells were cultured for 24 h in the presence of whole cells (WCs), cell walls (CWs), and cell-free extracts (CFEs) from various strains of Bifidobacterium and other lactic acid bacteria at various concentrations. The most effective component was different depending on the strains and the concentrations used. When tested with each cell fraction from Bifidobacterium sp. BGN4, heat treatment of the cell fractions lowered the production of IL-6. Synergistic effect was obtained, especially when CWs and CFEs were combined. Sonicated WCs stimulated IL-6 production more than intact WCs. The in vitro approaches employed here should be useful in further characterization of the effects of Bifidobacterium on gastrointestinal and systemic immunity.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.11.1-11.14
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• 2020

Most patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage of disease. Until recently, systemic treatment options that showed survival benefits in HCC have been limited to tyrosine kinase inhibitors, antibodies targeting oncogenic signaling pathways or VEGF receptors. The HCC tumor microenvironment is characterized by a dysfunction of the immune system through multiple mechanisms, including accumulation of various immunosuppressive factors, recruitment of regulatory T cells and myeloid-derived suppressor cells, and induction of T cell exhaustion accompanied with the interaction between immune checkpoint ligands and receptors. Immune checkpoint inhibitors (ICIs) have been interfered this interaction and have altered therapeutic landscape of multiple cancer types including HCC. In this review, we discuss the use of anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies in the treatment of advanced HCC. However, ICIs as a single agent do not benefit a significant portion of patients. Therefore, various clinical trials are exploring possible synergistic effects of combinations of different ICIs (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies) or ICIs and target agents. Combinations of ICIs with locoregional therapies may also improve therapeutic responses.

• BMB Reports
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• v.51 no.8
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• pp.371-372
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• 2018

Cardiovascular disease such as atherosclerosis is caused by imbalanced lipid metabolism and represents a leading cause of death worldwide. Epidemiological studies show that patients with systemic autoimmune diseases exhibit a higher incidence of atherosclerosis. Conversely, hyperlipidemia has been known to accelerate the incidence of autoimmune diseases in humans and in animal models. However, there is a considerable gap in our understanding of how atherosclerosis impacts the development of the autoimmunity in humans, and vice versa. The atherosclerosis-related autoimmune diseases include psoriasis, rheumatoid arthritis, systemic lupus erythematosus (SLE) and diabetes mellitus. By using animal models of atherosclerosis and SLE, we have recently demonstrated that hyperlipidemia significantly accelerates the development of autoantibodies, by inducing autoimmune follicular helper T ($T_{FH}$) cells. Mechanistic studies have identified that hyperlipidemia induces IL-27 production in a TLR4-dependent manner, likely via downregulating LXR expression in dendritic cells. In this case, mice lacking IL-27 do not develop enhanced antibody responses. Thus it is noted that these findings propose a mechanistic insight responsible for the tight association between cardiovascular diseases and SLE in humans.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.198-210
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• 2002

Background : Asthma is a chronic inflammatory disorder under immunological influence. Shinbi-tang and Gamishinbi-tang are herbal decoctions used for treating asthma in traditional herbal medicine. Objective : To evaluate the effects of Shinbi-tang and Gamishinbi-tang on immune cell & serum OA-specific IgE in broncho-alveolar lavage fluid (BALF) in rat asthma model. Material and Methods : Rats were sensitized with ovalbumin (OA); at day 1 sensitized group and Shinbi-tang and Gamishinbi-tang groups were systemically immunized by subcutaneous injection of 1mg OA and 300mg of Al(OH)$_3$ in a total volume of 2ml. At the same time, 1 ml of 0.9% saline containing 6 x 10$^{9}$ B. pertussis bacilli was injected by i.p. 14 days after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerosol containing 2%(wt/vol) OA. A day after local immunization, HAL fluid was collected from the rats. Rats were orally administered with each of Shinbi-tang and Gamishinbi-tang extract for 14 days from the day after local immunization. Lymphocyte, CD4+ T cell CD8+ T cell counts, CD4+/CD8+ ratio in BALF, change of serum OA-specific IgE level, CD4+ T cell CD8+ T cell percentages in the peripheral blood were measured and evaluated. Results : Shinbi-tang and Gamishinbi-tang showed an alleviating effect on asthmatic responses of rats. Shinbi-tang decreased total cell, lymphocyte, CD4+ T cell in BALF, serum OA-specific IgE level as compared with the control group. Gamishinbi-tang decreased total cell, lymphocyte, CD4+ T cell, and CD4+/CD8+ ratio in HALF as compared with the control group. CD4+/CD8+ ratio in HALF from Shinbi-tang group and serum OA-specific IgE level from Gamishinbi-tang group didn't show any significant variation from control group. CD8+ T cell in HALF, CD3+CD4+ T cell and CD3+CD8+ T cell percentages in peripheral blood showed no significant variation among groups. Conclusion : Shinbi-tang and Gamishinbi-tang alleviated asthmatic hypen-eactivity of the rat immune system through CD4+ T cell and serum IgE. Further the study of immune system modulating mechanism is expected.