• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.27 no.1
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• pp.26-36
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• 2024

Purpose: We investigated the role of CD8⁺T cells as host immune factors in pediatric patients with Helicobacter pylori gastritis. Methods: Gastric mucosal tissue and blood samples were collected from 39 children, including 11 children with H. pylori infection and 28 children as controls. Anti-CD8 and anti-T-bet antibodies were used for immunohistochemistry of the gastric mucosa. For the cell surface and intracellular staining, peripheral blood mononuclear cells were stained with anti-IL7Rα, anti-CX3CR1, anti-CD8, anti-T-bet, and anti-IFN-γ antibodies. Cytokines of sera such as tumor necrosis factor alpha (TNF-α) and CX3CL1 were analyzed using enzyme- linked immunosorbent assay (ELISA). Results: In the immunohistochemistry of gastric mucosa, the frequency of CD8⁺ and T-bet⁺ T cells cells was higher in the H. pylori-positive group than in the control group (26.9± 7.8% vs. 16.9±3.3%, p<0.001; 5.0±2.5% vs. 2.2±0.7%, p=0.001). Between the control and H. pylori-positive groups, the frequency of IL-7Rα^lowCX3CR1⁺ CD8⁺ and T-bet⁺ INF-γ⁺ CD8⁺ T cells were not significantly different between surface and intracellular staining, respectively (40.4±24.0% vs. 38.2±17.8%, p=0.914; 40.4±24.0% vs. 38.2±17.8%, p=0.914). In the ELISA, no significant differences in TNF-α and CX3CL1 concentrations were observed between the control and H. pylori-positive groups (34.3±12.1 pg/mL vs. 47.0±22.6 pg/mL, p=0.114/0.5± 0.1 pg/mL vs. 0.5±0.1 pg/mL, p=0.188). Conclusion: CD8⁺ T and Th1 cells, which secrete IFN-γ, might play important roles in the mucosal immunity of the stomach in children with H. pylori infection.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.135-146
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• 2001

Background : One of the important mechanisms responsible for a tumor escaping the immune response is an absence of the tumor associated antigen (TAA) on the cancer cell surface. To overcome this, combination gene therapy using a herpes simplex thymidine kinase (HSTK) gene, prototype of drug sensitizing gene, was conducted to enhance T AA release by cell destruction, as well as the cytokine genes for immune cell attraction. Methods : We investigated whether or not transduction with the adenovirus-HSTK (Ad-HSTK) enhanced the sensitivity of Lewis lung carcinoma (LLC) to ganciclovir (GCV) and induced a bystander effect. A Tumor vaccine trial was performed using LLC with ad-HSTK$\pm$ad-GM-CSF$\pm$ad-IL-2 to determine if they exhibit some antitumor effect on established lung cancer xenografts. Results : LLC with ad-HSTK revealed a much higher sensitivity to ganciclovir (GCV). LLC transduced with ad-HSTK and/or ad-IL-2, ad-GM-CSF showed a lower in vivo tumorigenicity. In the treatment experiment, vaccination with LLC transduced with ad-HSTK, ad-IL-2, or ad-GM-CSF alone modestly suppressed the growth of an established tumor. Combined transduction with HSTK and GM-CSF induced stronger growth suppression of a established lung cancer, while HSTK and IL-2 combination transduction did not have any antitumor effect on individual transduction. Vaccination with LLC-HSTK-GM-CSF increased the infiltration of dendritic cells in the spleen. Conclusion : It was concluded that a tumor vaccine transduced with HSTK and GM-CSF induces strong antitumor immunity by activating the dendritic cells.

• Food Science and Biotechnology
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• v.14 no.4
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• pp.479-486
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• 2005

Arabinoxylan, a complex polysaccharide in cereal cell walls, has recently received research attention as a biological response modifier. The immunomodulating effect of arabinoxylans from rice bran (AXrb) was studied using a combined process of extrusion and commercial hemicellulase treatment in order to elucidate the augmentation mechanism of cell-mediated immunity in vitro. The cytotoxicity of mouse spleen lymphocytes against YAC-1 tumor cells was significantly enhanced by treatment with AXrb at $10-100\;{\mu}g/mL$. In an attempt to investigate the mechanism by which AXrb enhance NK cytotoxicity, we examined the effect of AXrb on cytokine production by spleen lymphocytes. Culture supernatants of the cells incubated with AXrb were collected and analyzed for IL-2 and IFN-${\gamma}$ synthesis by ELISA. IL-2 and IFN-${\gamma}$ production were increased significantly. These results suggest that AXrb may induce Th1 immune responses. Macrophages play an important role in host defenses against tumors by killing them and producing secretory products, which protect against bacterial, viral infection and malignant cell growth. AXrb were examined for their ability to induce secretory and cellular responses in murine peritoneal macrophages. When macrophages were treated with various concentrations ($10-100\;{\mu}g/mL$) of AXrb, AXrb induced tumoricidal activity, as well as increasing phagocytosis and the production of NO, $H_2O_2$, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. These results indicate that reactive oxygen species, reactive nitrogen species, and inflammatory cytokines are likely to be the major mediators of tumoricidal activity in AXrb-treated macrophages. Therefore, AXrb may be useful in cancer immunotherapy and it is anticipated that AXrb obtained using extrusion and subsequent enzyme treatment can be used as an ingredient in nutraceuticals and cereal-based functional food.

• Natural Product Sciences
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• v.24 no.3
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• pp.194-198
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• 2018

Inflammation is a biological response caused by overactivation of the immune system and is controlled by immune cells via a variety of cytokines. The overproduction of pro-inflammatory cytokines enhances abnormal host immunity, resulting in diseases such as rheumatoid arthritis, cardiovascular disease, Alzheimer's disease, and cancer. Inhibiting the production of pro-inflammatory cytokines such as interleukin (IL)-12p40, IL-6, and tumor necrosis factor $(TNF)-{\alpha}$ might be one way to treat these conditions. Here, we investigated the anti-inflammatory activity of compounds isolated from Cimicifuga dahurica (Turcz.) Maxim., which is traditionally used as an antipyretic and analgesic in Korea. In primary cell culture assays, 12 compounds were found to inhibit the production of pro-inflammatory cytokines (IL-12p40, IL-6, and $TNF-{\alpha}$) in vitro in bone marrow-derived dendritic cells stimulated with LPS.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.8
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• pp.1095-1101
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• 2016

Ginsenoside Rg1 is a natural compound with various efficacies and functions. It has beneficial effects on aging, diabetes, and immunity, as well as antioxidant and proliferative functions. However, its effect on porcine embryo development remains unknown. We investigated the effect of ginsenoside Rg1 on the in vitro development of preimplantation porcine embryos after parthenogenetic activation in high-oxygen conditions. Ginsenoside treatment did not affect cleavage or blastocyst formation rates, but did increase the total cell number and reduced the rate of apoptosis. In addition, it had no effect on the expression of four apoptosis-related genes (Bcl-2 homologous antagonist/killer, B-cell lymphoma-extra large, Caspase 3, and tumor protein p53) or two metabolism-related genes (mechanistic target of rapamycin, carnitine palmitoyltransferase 1B), but increased the expression of Glucose transporter 1 (GLUT1), indicating that it may increase glucose uptake. In summary, treatment with the appropriate concentration of ginsenoside Rg1 ($20{\mu}g/mL$) can increase glucose uptake, thereby improving the quality of embryos grown in high-oxygen conditions.

• Korean Journal of Oriental Medicine
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• v.16 no.2
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• pp.131-141
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• 2010

Objective : Benign prostatic hyperplasia(BPH) is one of the most common diseased among elderly men. BPH can be treated with alpha-1 adrenergic blocker or $5{\alpha}$-reductase inhibitor(Finasteride) that reduces serum dihydrotestosterone(DHT). Phellodendri Cortex Ex has been broad studied on its chemical components, pharmacological activity, and clinical effects on anti-inflammation, anti-allergy, anti-tumor, immunity, antibacteria and other bioactivities. In this study, we investigated the therapeutic effects and action mechanism of Phellodendri Cortex Ex with a BPH induced by castration and testosterone treatment. Methods : Sprague-Dawley rats were treated with testosterone after castration for induction of experimental benign prostatic hyperplasia, which is similar to human benign prostatic hyperplasia in histopathological profiles. Phellodendri Cortex as an experimental specimen, and Finasteride as a positive control, were administered orally. The prostates were evaluated by histopathological changes, and the expression of $5{\alpha}$-reductase genes. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Phellodendri Cortex Ex showed a diminished range of the tissue damage. In the reverse transcription-polymerase chain reaction(RT-PCR) of $5{\alpha}$-reductase genes, Phellodendri Cortex inhibited the expression of $5{\alpha}$-reductase genes. Conclusions : These findings suggest that Phellodendri Cortex Ex may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the suppression of $5{\alpha}$-reductase. From these results, we suggest that Phellodendri Cortex Ex could be a useful agent for treating the benign prostatic hyperplasia.

• Journal of Microbiology and Biotechnology
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• v.28 no.2
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• pp.218-226
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• 2018

Nanometric Lactobacillus plantarum nF1 (nLp-nF1) is a biogenics consisting of dead L. plantarum cells pretreated with heat and a nanodispersion process. In this study, we investigated the immune-enhancing effects of nLp-nF1 in vivo and in vitro. To evaluate the immunostimulatory effects of nLp-nF1, mice immunosuppressed by cyclophosphamide (CPP) treatment were administered with nLp-nF1. As expected, CPP restricted the immune response of mice, whereas oral administration of nLp-nF1 significantly increased the total IgG in the serum, and cytokine production (interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-${\alpha}$)) in bone marrow cells. Furthermore, nLp-nF1 enhanced the production of splenic cytokines such as IL-12, TNF-${\alpha}$, and interferon gamma (IFN-${\gamma}$). In vitro, nLp-nF1 stimulated the immune response by enhancing the production of cytokines such as IL-12, TNF-${\alpha}$, and IFN-${\gamma}$. Moreover, nLp-nF1 given a food additive enhanced the immune responses when combined with various food materials in vitro. These results suggest that nLp-nF1 could be used to strengthen the immune system and recover normal immunity in people with a weak immune system, such as children, the elderly, and patients.

• Journal of Microbiology and Biotechnology
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• v.9 no.1
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• pp.98-105
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• 1999

Intestinal bacteria comprise one-third of the contents of the large intestine in humans. Their interactions with the gastrointestinal immune system induce characteristic immunological responses which stimulate or suppress the host's defense system. RAW 264.7 murine cell line was used as a macrophage model to assess the effects of the exposure to the isolated human intestinal bacteria, Bacteroides, Bifidobacterium, Eubacterium, Streptococcus, and E. coli, on NO (nitric oxide), $H_2O_2$(hydrogen peroxide), and cytokines IL (interleukin)-6 and TNF (tumor necrosis factor)-a production. RAW 264.7 cells were cultured in the presence of heat-killed bacteria for 24 h at concentrations of 0-$50\mu$g/ml. Our results showed that Bacteroides and E. coli stimulated IL-6, TNF-$\alpha$, NO, and $H_2O_2$production at high levels even at $1\mu$g/ml, whereas Bifidobacterium, Eubacterium, and Streptococcus showed a low level of stimulation at $1\mu$g/ml, and a gradual increase as the cell concentration increased up to $50\mu$g/ml. This result suggests that gram-negative Bacteroides and E. coli are better able to stimulate macrophage than gram-positive Bifidobacterium, Streptococcus, and Eubacterium. The in vitro approaches employed here should be useful in further characterization of the effects of intestinal bacteria on gastrointestinal and systemic immunity.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6233-6239
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• 2013

Diabetes represents a serious health problem. In the diabetic state, alterations in metabolism, increased susceptibility to infections and immunological changes occur. The suppression of the immune response has been identified as a relevant factor that contributes to the increase in the rate of infections in these patients. At the same time, breast cancer is the most frequent malignant tumor in women. The molecular and cellular mechanisms underlying cancer development have revealed that immune cells functionally regulate epithelial cancer development and progression. Breastfeeding has been hypothesized to reduce the risk of breast cancer. However, early systematic reviews have not yielded consistent findings for this association. The demand for human milk is increasing due to the promotion and consumer acceptance of the health benefits of consuming a natural product rich in bioactive components. However, due to changes in glucose metabolism, the components of the milk from diabetic women are modified depending on the time of evaluation. In this literature review, we summarize important new findings revealing the paradoxical role of breastfeeding in preventing the onset of breast cancer in diabetic mothers. We hypothesized that the milk component production in diabetic mothers is affected by changes in glucose metabolism. Therefore, adequate maternal glycemic control and an adequate duration of breastfeeding for diabetic mothers are crucial to ensure that the immunity components are able to confer protection against breast cancer.

• IMMUNE NETWORK
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• v.7 no.2
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• pp.57-65
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• 2007

Background: Cordyceps militaris have been reported to modify the immune and inflammatory responses both in vivo and in vitro. Macrophages play important roles in the innate immunity through the phagocytosis of antigens. This study examined the effects of Cordyceps militaris on the activation of murine macrophage RAW 264.7 cells and primary macrophages. Methods: The components contained in culture broth of Cordyceps militaris were purified by propyl alcohol extraction and HP 20 column chromatography to CMDB, CMDBW, CMDB5P, and CMDB25P. The amounts of nitric oxide (NO) were determined by using ELISA, Griess reagent respectively. The amounts of some cytokines were determined by using ELISA, western blot, and RT-PCR The expression levels of cell surface molecules (ICAM-1, B7-1 and B7-2) were measured by flow cytometric analysis. Results: All the components of Cordyceps militaris produced significant amounts of NO. In particular, CMDB produced much more NO in RAW 264.7 cells and primary macrophages than other fractions of Cordyceps militaris. CMDB increased significantly the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$, and IL-6 dose-dependently in RAW 264.7 cells. Examination of the gene expression level also showed that the enhanced production of cytokines was correlated with the up-regulation of i-NOS expression, cycloxygenase (COX)-2 expression, IL-1${\beta}$ and IL-6 expression, and TNF-${\alpha}$ expression on the expression of mRNAs by semi-quantitative RT-PCR Western blot analysis also confirmed that CMDB enhances the expression level of these cytokines. Conclusion: These results show that CMDB stimulates the production of NO and pro-inflammatory cytokines and can also up-regulate the gene expression levels in macrophages.