• BMB Reports
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• v.35 no.6
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• pp.537-546
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• 2002

NF-${\kappa}B$/Rel transcription factor family participates in diverse biological processes including embryo development, hematopoiesis, immune regulation, as well as neuronal functions. In this review, the NF-${\kappa}B$/Rel signal transduction pathways and their important roles in the regulation of immune system will be discussed. NF-${\kappa}B$/Rel members execute distinct functions in multiple immune cell types via the regulation of target genes essential for cell proliferation, survival, effector functions, cell trafficking and communication, as well as the formation of lymphoid architecture. Consequently, proper activation of NF-${\kappa}B$/Rel during immune responses to allergens, auto-antigens, allo-antigens, and pathogenic infection is crucial for the integrity of host innate and adaptive immunity.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.12 no.1
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• pp.79-98
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• 1999

The purpose of this Study was to investigate effect of TakliSodokSan(TSS) on the anti-tumor, immunocytes and nitric oxide(NO) production from mice peritoneal macrophages. This Study estimated the proliferation of L1210 cell lines, A431 cell lines, Hep-G2 cell lines, K562 cell lines, 3T3 cell lines, mouse thymocytes and mouse splenocytes and NO production from pcritoneal macrophages in vitro, and estimated the proliferation of L1210 cells, thymocytes and splenocytcs, NO production from peritoneal macrophages and body weight in L1210 cells-transplanted mice in vivo. The results were obtained as follows; 1. TSS inhibited significantly the proliferation of L1210, A431, Hep-G2, K562 cell lines in vitro. 2. TSS accelerated the proliferation of mice thymocytes and splenocytes in vitro. 3. TSS was not increased the nitric oxide production from mice peritoneal macrophages in vitro. 4. TSS inhibited significantly the proliferation of L1210 cells in Ll210 cells∼transplanted mice. 5. TSS accelerated the proliferation of mice thymocytes and splenocytes In L1210 cells-transplanted mice. 6. TSS was increased significantly the nitric oxide production from mice peritoneal macrophages in L1210 cells-transplanted mice. 7. TSS was increased the body weight as comparing with control group in Ll210 cells-transplanted mice.

• Food Science of Animal Resources
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• v.42 no.5
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• pp.903-914
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• 2022

Probiotics are currently considered as one of tools to modulate immune responses under specific clinical conditions. The purpose of this study was to evaluate whether oral administration of three different probiotics (Lactiplantibacillus plantarum CJLP243, CJW55-10, and CJLP475) could evoke a cell-mediated immunity in immunodeficient mice. Before conducting in vivo experiments, we examined the in vitro potency of these probiotics for macrophage activation. After co-culture with these probiotics, bone marrow derived macrophages (BMDMs) produced significant amounts of proinflammatory cytokines including interleukin-6 (IL-6), IL-12, and tumor necrosis factor-α (TNF-α). Levels of inducible nitric oxide synthase (inos) and co-stimulatory molecules (CD80 and CD86) were also upregulated in BMDMs after treatment with some of these probiotics. To establish an immunocompromised animal model, we intraperitoneally injected mice with cyclophosphamide on day 0 and again on day 2. Starting day 3, we orally administered probiotics every day for the last 15 d. After sacrificing experimental mice on day 18, splenocytes were isolated and co-cultured with these probiotics for 3 d to measure levels of several cytokines and immune cell proliferation. Results clearly indicated that the consumption of all three probiotic strains promoted secretion of interferon-γ (IFN-γ), IL-1β, IL-6, IL-12, and TNF-α. NK cell cytotoxicity and proliferation of immune cells were also increased. Taken together, our data strongly suggest that consumption of some probiotics might induce cell-mediated immune responses in immunocompromised mice.

• YAKHAK HOEJI
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• v.51 no.4
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• pp.270-276
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• 2007

Silybin is known to be a major active flavonoid component isolated from Silybum marianum, a hepatoprotective medicinal plant. In this study, we examined the immunomodulatory role of silybin on T cell and macrophage-mediated immune responses. To do this, the proliferation of splenic lymphocytes and CD8+ CTLL-2 cells under mitogenic stimulation with lipopolysaccharide (LPS), concanavalin (Con) A and interleukin (IL)-2 and the production of $TNF-{\alpha}$ and NO from LPS- and $IFN-{\gamma}$-activated macrophages was evaluated under silybin treatment. The mitogenic proliferation of splenic lymphocytes induced by LPS and Con A was strongly diminished by silybin in a dose-dependent manner. Moreover, the proliferation of CD8+ CTLL-2 cells was also negatively modulated by the compound. In contrast, silybin did not strongly suppress the proliferation of normal splenocytes and T cell line Sup-T1 cells, indicating that the inhibitory effect of silybin may be due to blocking only mitogenic responses of splenic lymphocytes. In addition, silybin inhibited $TNF-{\alpha}$ production in LPS-stimulated RAW264.7 cells. Effect of silybin however was distinct, according to NO-inducing stimuli. Thus, silybin only blocked NO production induced by $IFN-{\gamma}$ but not LPS and the inhibition was increased when PMA was co-treated with $IFN-{\gamma}$. Unlike NO inhibition, however, this compound protected the cytotoxic damage of RAW264.7 cells induced by both LPS and $IFN-{\gamma}$. Therefore, our data suggest that silybin may participate in host immune responses mediated by T cells and macrophages via regulating mitogenic proliferation, and the production of $TNF-{\alpha}$ and NO, depending on cellular stimuli.

• The Korea Journal of Herbology
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• v.25 no.4
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• pp.23-29
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• 2010

Objectives : To investigate the immunological activities, we evaluated the combination ratio of Aconiti Lateralis Radix Preparata and Glycyrrhizae Radix (AG) on murine macrophage cell line (RAW 264.7) and ovalbumin/aluminium (OVA/Alum)-immunized mice. Methods : The cellular proliferation and the production of nitric oxide were examined in a macrophage cell line, RAW 264.7 cells, in the presence of the combination ratio of Aconiti Lateralis Radix Preparata and Glycyrrhizae Radix. C57BL/6 mice were immunized intraperitonially with ovalbumin/aluminium ($100{\mu}g/200{\mu}g$) on day 1, 8, and 15. The combination ratio of Aconiti Lateralis Radix Preparata and Glycyrrhizae Radix (1 g/kg/day) was orally administrated for 3 weeks. On day 22, splenocyte and plasma were collected for mitogen-induced proliferation, lymphocyte subpopulation by flow cytometry and measurement of AST (Aspirate aminotransferase), ALT (Alanine aminotransferase), and antibodies (OVA-specific antibodies of the IgG, IgG1, and total IgM classes). Results : Aconiti Lateralis Radix Preparata treatment had no influence on immune responses. The proliferation and NO production of macrophage and proliferation of splenocyte were increased as the higher ratio of Glycrrhizae Radix. The proliferation of splenocyte, lymphocyte subpopulation and production of antibody (total IgM, OVA-specific IgG and OVA-specific IgG1) were increased as the higher ratio of Glycrrhizae Radix on OVA-immunzed mice. Conclusions : These results suggest that the higher ratio of Glycyrrhizae Radix can increase immunological activities such as NO production in RAW264.7 cells, splenocyte proliferation and immunoglobulin production in OVA-immunized mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.11
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• pp.1759-1762
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• 2015

Tarak is a Korean traditional fermented milk product that is fermented by adding rice wine to milk. Tarak was produced with Lactobacillus paracasei ssp. paracasei M13-65-3 isolated from rice wine, and its effects on immune cell proliferation and melanin biosynthesis were investigated. Tarak extract significantly increased proliferation of T lymphocyte Jurkat clone E6-1 cells at concentrations from 10 to $100{\mu}g/mL$. Tarak inhibited activities of tyrosinase and ${\alpha}$-melanocyte-stimulating hormone-induced melanin biosynthesis in mouse skin B16-F10 cells at a concentration of $100{\mu}g/mL$. These results suggest that tarak might have functionalities for enhancing the immune system by increasing immune cell proliferation and regulating melanin biosynthesis.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.455-462
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• 2018

Background: Ginsenoside Rh2 has been known to enhance the activity of immune cells, as well as to inhibit the growth of tumor cells. Although the repertoire of genes regulated by Rh2 is well-known in many cancer cells, the epigenetic regulation has yet to be determined, especially for comprehensive approaches to detect methylation changes. Methods: The effect of Rh2 on genome-wide DNA methylation changes in breast cancer cells was examined by treating cultured MCF-7 with Rh2. Pyrosequencing analysis was carried out to measure the methylation level of a global methylation marker, LINE1. Genome-wide methylation analysis was carried out to identify epigenetically regulated genes and to elucidate the most prominent signaling pathway affected by Rh2. Apoptosis and proliferation were monitored to examine the cellular effect of Rh2. Results: LINE1 showed induction of hypomethylation at specific CpGs by 1.6-9.1% (p < 0.05). Genome-wide methylation analysis identified the "cell-mediated immune response"-related pathway as the top network. Cell proliferation of MCF-7 was retarded by Rh2 in a dose-dependent manner. Hypermethylated genes such as CASP1, INSL5, and OR52A1 showed downregulation in the Rh2-treated MCF-7, while hypomethylated genes such as CLINT1, ST3GAL4, and C1orf198 showed upregulation. Notably, a higher survival rate was associated with lower expression of INSL5 and OR52A1 in breast cancer patients, while with higher expression of CLINT1. Conclusion: The results indicate that Rh2 induces epigenetic methylation changes in genes involved in immune response and tumorigenesis, thereby contributing to enhanced immunogenicity and inhibiting the growth of cancer cells.

• YAKHAK HOEJI
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• v.58 no.2
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• pp.81-90
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• 2014

In order to determine the functional benefits of Cordyceps militaris in the immune system, we examined the immunomodulatory activities of C. militaris using an immunocompromised C57BL/6 mice, mouse spleen cells, RAW 264.7 macrophage cells, and A549 lung carcinoma cells. Mice were injected intraperitioneally with an immunosuppressive drug, cyclophosphamide, and then administered orally with 30, 100 and 300 mg/kg of 50% ethanol extract of C. militaris (CME 30, CME 100 and CME 300) for 14 days. CME increased splenocyte proliferation and natural killer (NK) cell activity compared to 3% hydroxypropyl methylcellulose-treated control mice. CME also increased the production of Th1 cytokines, IL-2 and TNF-${\alpha}$ in spleen cells isolated from CME-injected mice and in vitro, which suggested the enhanced cellular immunity in response to CME. CME also increased splenocyte proliferation, NK cell activity, and IL-2 and TNF-${\alpha}$ production compared to 1 ${\mu}M$ methotrexate-treated spleen cells in vitro. We examined whether C. militaris regulates the production of inflammatory mediators in LPS-stimulated RAW 264.7 cells. CME inhibited LPS-induced NO production and iNOS expression in a dose dependent manner, while COX-2 expression was remained unchanged. In addition, CME also has free radical scavenging activity, indicating its antioxidant activity. These results indicate that C. militaris enhances immune activity by promoting immune cell proliferation and cytokine production.

• IMMUNE NETWORK
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• v.6 no.2
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• pp.86-92
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• 2006

Background: Germanium compounds are increased to use in nutrient foods and medicines in terms of antibiotics to microbes, anticancer, modulation of immune system and neutralizing heavy metal toxins. Geranti Bio-Ge Yeast, containing stable organic germanium and bound to the yeast protein was developed by Geranti Pharm. LTD. and the modulation effect in the immune system was examined in vivo and in vitro. Methods: The compound, Geranti Bio-Ge Yeast, was fed to female Balb/c mice (each group has 10 mice) for 4 weeks and the yeast powder and steamed red ginseng powder were used as control during the same feeding time points. During 4 weeks there was no symptom to be considered, and after 4 weeks feeding all mice were sacrificed to check the changes of related immune cells and subsidiary responses (i.e. cell counting, FACS, MTT, LDH, PFC assay). Results: In pre-post comparison, B cell population was increased in the group of Geranti Bio-Ge Yeast in a dose dependent manner (100 to 800 mg/kg). However, the population of T cell, dendritic cell and macrophage was not comparably changed in all doses. The ability of cytokine production and proliferation was almost same level as shown in control group. In contrast, PFC assay informed that the compound increase the antibody production ability when fed over 200 mg/kg implying that the increase of PFC number might be due to the increase of B cells. Conclusion: Over the entire study, we concluded that the compound, Geranti Bio-Ge Yeast has better potential in immune response in terms of B cell proliferation than that of positive control, red ginseng, and the compound can be one of the future candidates for a new supplementary source improving immune system activity.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.5.1-5.22
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• 2022

The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.