• Journal of Microbiology and Biotechnology
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• v.23 no.7
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• pp.1023-1030
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• 2013

Lipoteichoic acid (LTA), uniquely expressed on gram-positive bacteria, is recognized by Toll-like receptor 2 (TLR2) on not only antigen-presenting cells but also activated T cells. Therefore, it is reasonable to assume that LTA is acting on T cells. However, little is known about the effect of LTA on T-cell regulation. In the present study, we investigated the immunomodulatory effects of LTA on $CD4^+$ T cells. Effector $CD4^+$ T cells, induced after co-culture with S. aureus-pulsed dendritic cells, produced high levels of interferon-${\gamma}$, CD25, CD69, and TLRs 2 and 4. When effector $CD4^+$ T cells were treated with LTA, the expressions of the membrane-bound form of transforming growth factor (TGF)-${\beta}$ and forkhead box P3 increased. Coincidently, the proliferation of effector $CD4^+$ T cells was declined after LTA treatment. When TGF-${\beta}$ signaling was blocked by the TGF-${\beta}$ receptor 1 kinase inhibitor, LTA failed to suppress the proliferation of effector $CD4^+$ T cells. Therefore, the present results suggest that LTA suppresses the activity of effector $CD4^+$ T cells by enhancing TGF-${\beta}$ production.

• BMB Reports
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• v.41 no.11
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• pp.814-819
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• 2008

Interleukin-32 (IL-32) induces a variety of proinflammatory cytokines and chemokines. The IL-32 transcript was reported originally in activated T cells; subsequently, it was demonstrated to be abundantly expressed in epithelial and endothelial cells upon stimulation with inflammatory cytokines. IL-32 is regulated robustly by other major proinflammatory cytokines, thereby suggesting that IL-32 is crucial to inflammation and immune responses. Recently, an IL-32$\alpha$-affinity column was employed in order to isolate an IL-32 binding protein, neutrophil proteinase 3 (PR3). Proteinase 3 processes a variety of inflammatory cytokines, including TNF$\alpha$, IL-$1{\beta}$, IL-8, and IL-32, thereby enhancing their biological activities. In the current study, we designed four PR3-cleaved IL-32 separate domains, identified by potential PR3 cleavage sites in the IL-32$\alpha$ and $\gamma$ polypeptides. The separate domains of the IL-32 isoforms $\alpha$ and $\gamma$ were more active than the intrinsic $\alpha$ and $\gamma$ isoforms. Interestingly, the N-terminal IL-32 isoform $\gamma$ separate domain evidenced the highest levels of biological activity among the IL-32 separate domains.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.358-366
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• 2024

The lactic acid bacteria, including Latilactobacillus sakei and Latilactobacillus curvatus, have been widely studied for their preventive and therapeutic effects. In this study, the underlying mechanism of action for the antioxidant and immunostimulatory effects of two strains of heat-treated paraprobiotics was examined. Heat-treated L. sakei KU15041 and L. curvatus KU15003 showed higher radical scavenging activity in both the 2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assays than the commercial probiotic strain LGG. In addition, treatment with these two strains exhibited immunostimulatory effects in RAW 264.7 macrophages, with L. curvatus KU15003 showing a slightly higher effect. Additionally, they promoted phagocytosis and NO production in RAW 264.7 cells without any cytotoxicity. Moreover, the expression of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 was upregulated. These strains resulted in an increased expression of inducible nitric oxide synthase and cyclooxygenase-2. Moreover, the nuclear factor-κB and mitogen-activated protein kinase signaling pathways were stimulated by these strains. These findings suggest the potential of using L. sakei KU15041 and L. curvatus KU15003 in food or by themselves as probiotics with antioxidant and immune-enhancing properties.

• KSBB Journal
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• v.23 no.2
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• pp.109-117
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• 2008

Phellinus linteus (Sang Hwang mushroom; P. linteusis) has been widely used for a traditional medicine in Japan, Korea and China. In traditional oriental applications, P. linteus and their extracts have been exclusively used to treat various diseases like insomnia, neurasthenia, gastric ulcers, arthritis, nephritis, stress, asthma, bronchitis, neuromuscular disorders, hypertension and also as an immune system stimulator in cancer therapy. In a number of articles, it is indicated how tremendous their therapeutic values are. According to these studies, P. linteus and their extracts show immunomodulatory activities like enhancing immune system function including anti-tumor activity and inhibiting the growth of existing tumors. P. linteus and their extracts have been being studied for use as immunotherapy agents and biological response modifiers (BRMs) for the possible treatment of cancer without side effects. Recently, the cultured mycelium product of P. linteus has been developed and approved as a medicine in Korea. This review shows not only the current status of methods of developmental technology like artificial culture and various biological applications of P. linteus but also recent market trends of functional foods made from P. linteus.

• The Korea Journal of Herbology
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• v.32 no.4
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• pp.1-8
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• 2017

Objectives : Silkworm is known as immunomodulatory substances and contain various bioactive compounds such as serine, tyrosine and alanine. The aim of this study was to investigated the immunopotentiating activity of combine extract that silkworm and food materials (Eucommia ulmoides, Angelica gigas, Acanthopanax, Allium hookeri, Cinnamomum cassia, Liriope platyphylla, Curcuma longa, Achyranthes japonica, Alpinia oxyphylla, Adenophora triphylla). Methods : Among 10 kinds of food materials, to select food materials with the effect of enhancing the immune function mouse splenocyte proliferation ability was measured by 3-[4,5-dimethylthiazol-2-y]-2,5-diphenyl terazolium bromide (MTT) assay. Then, combine extract of silkworm and food materials were evaluated that mouse splenocyte proliferation ability by EZ-cytox cell viability assay. Morever, cytokines production such as IL-2, IL-4, IL10, IL12, $IFN-{\gamma}$ on mouse T lymphocyte stimulated with concanavalin A (ConA) was measured. Results : Eucommia ulmoides, Acanthopanax, Allium hookeri, Cinnamomum cassia, Liriope platyphylla has high proliferation ability of mouse splenocyte compared with Curcuma longa, Achyranthes japonica, Alpinia oxyphylla, Adenophora triphylla. The silkworm and food material combined extract has a relatively high proliferation ability of mouse splenocyte proliferation when the silkworm and food materials are used as a single material. In particularly, combined extract of silkworm and Cinnamomum cassia was stimulate cytokine production on T lymphocyte such as IL12, $IFN-{\gamma}$. Combined extract of silkworm and Liriope platyphylla was stimulate cytokine production on T lymphocyte such as IL2, IL4, IL10. Conclusion : In conclusion, the combined extract of the silkworm and Cinnamomum cassia or Liriope platyphylla may enhance immune function by regulating mouse splenocyte proliferation and stimulating cytokine production.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.1
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• pp.1-7
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• 2017

Zerumbone is a major component of the essential oil from Zingiber zerumbet Smith, which is a kind of wild ginger. In addition, various biological functions, such as liver protection, pain relief, atherosclerosis, and antimicrobial activity have been reported. It is also known to be effective in the proliferation of immune cells and the expression of cytokines. In this study, we investigated the effects of zerumbone on monocyte activation. First, it was confirmed that the proliferation of THP-1 cells was increased by zerumbone. The strongest increase in THP-1 proliferation after lipopolysaccharide treatment was observed at $5{\mu}M$ zerumbone treatment, and the increase of cell proliferation without lipopolysaccharide was the highest at $10{\mu}M$. Conversely, when treated with $50{\mu}M$ zerumbone, a rapid decrease of proliferation was observed regardless of the presence of lipopolysaccharide (LPS). The phosphorylation of signaling protein, Erk, induced by LPS was also increased by zerumbone. The strongest increase in phosphorylation was observed when treated with $50{\mu}M$ of zerumbone with reduced proliferation. The activity of transcription factor $NF-{\kappa}B$ was not significantly altered by zerumbone alone, but increased when treated with lipopolysaccharide. Furthermore, the transcription of the inflammatory cytokines $TNF-{\alpha}$ and IL-8, which are regulated by $NF-{\kappa}B$, is also increased by zerumbone. These results suggest that zerumbone can enhance the proliferation and activity of monocytes. Furthermore, it is believed that zerumbone can enhance rthe immune responses through increased monocyte activity in bacterial infections with LPS, thereby helping to treat effective bacteria.

• Food Science and Preservation
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• v.30 no.6
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• pp.1082-1094
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• 2023

The purpose of this study was to examine the characteristics of Leuconostoc spp. isolated from radish kimchi and to investigate the potential for the use of functional ingredients by evaluating enzymatic characteristics, safety, and immune-enhancing effects among the isolates, including Lactobacillus rhamnosus ATCC53103 (LGG) as a control strain. All test strains exhibited β-glucosidase enzyme activity that releases β-1,4 sugar chain bonds. In addition, as a result of antibiotic resistance assay among the isolates, MIC values on 8 antibiotics were below compared to the EFSA standard, and hemolytic experiments confirmed that all showed gamma hemolysis without hemolytic ability. As a result of the antibacterial activity experiment, the Leu. mesenteroides K2-4 strain showed a higher activity than LGG against Bacillus cereus and Staphylococcus aureus. Additionally, the activity of the NF-kB/AP-1 transcription factor increased when the isolates were treated in macrophage RAW cells. These results were related to increasing the high mRNA expression levels on TNF-α and IL-6 by Leu. mesenteroides K2-4 strain to be treated at low concentration. Consequently, we suggest that it will be useful as a candidate for functional food ingredients.

• BMB Reports
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• v.51 no.11
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• pp.572-577
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• 2018

Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1021-1027
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• 2004

Panax ginseng has been used as a typical tonic medicine in Asian countries, such as Korea, China, and Japan. It has been reported that ginsenoside Rg1 in Panax ginseng increases the proportion of T helper cells in the whole T cells and promotes IL-2 gene expression in murine splenocytes. These studies imply that ginsenoside Rg1 increases the immune activity of CD4+ T cell, however the exact mechanism of ginsenoside Rg1 on helper T cell remains to be verified. The present study tried to elucidate the direct effect of Rg1 on helper T cell s activities and its Th1/Th2 lineage development. The results demonstrated that ginsenoside Rg1 had not mitogenic effects on the unstimulated CD4+ T cell, but augmented CD4+ T cell proliferation upon activating with anti-CD3/anti-CD28 antibodies in a dose dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4+ T cell. In Th0 condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4+ T cells, suggesting Rg1 prefer to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secreting CD4+ T cell under Th2 skewed condition, while decreases IFN-γ secreting cell in Th1 polarizing condition. Thus, Rg1 enhances Th2 lineage development from naive CD4+ T cell both by increasing Th2 specific cytokine secretion and by repressing Th1 specific cytokine production. Therefore, these results suggest that ginsenoside Rg1 might be desirable agent for enhancing CD4+ T cell's activity, as well as the correction of Th1 dominant pathological disorders.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.6
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• pp.1283-1286
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• 2001

Effect of the egg yolks from laying hens intubated, p.o., astaxanthin (designated AEY) on mouse humoral immunity was investigated using male ICR mouse (6~7 weeks of age). Mice were adapted in a temperature- and humidity- controlled house for one week and randomly divided into 5 treatment groups (9 mice/cage/treatment). Mice were intubated p.o., AEY (100, 250 and 500$\mu\textrm{g}$) or control egg yolks (CEY, 250$\mu\textrm{g}$), dissolved in 0.1 mL DMSO, for consecutive 4 days. At day 5, carbon suspension (pilot drawing ink 3 mL+3% gelatine 3 mL) was injected 3 $\mu$L Per 1 g body weight through tail vein. Carbon clearance time was measured at 5 and 35 minutes Post the injection of carbon suspension. Another two experiments were conducted to determine the hemagglultinin-titer (HGT) and hemolysin-titer (HLT) with male ICR mouse (8 mice/cage/treatment). Mice treated with AEY were induced immune activity with SRBC. HGT and HLT were measured from the blood at day 1 and 3 after treatment of SRBC. AEY treatment reduced the carbon clearance time. Especially the carbon clearance time by 500 $\mu\textrm{g}$ AEY treatment was 5.00 minutes, which was very short time compared with 9.42 minutes by control and 9.01 minutes by CEY. AEY group showed slights higher values of HGT and HLT than CEY group and control. At day 1, HGT in control, 250$\mu\textrm{g}$ CEY and 250$\mu\textrm{g}$ AEY groups was 5.50, 5.63, and 6.00, respectively. Similiarly, HLT in control, 250$\mu\textrm{g}$ CEY and 250$\mu\textrm{g}$ AEY groups was 4.75, 5.38, and 5.50, respectively, at day 1. These results suggest that AEY exhibited immunity-enhancing effect.