• The Korean Journal of Physiology and Pharmacology
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• v.7 no.5
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• pp.255-259
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• 2003

Dendritic cells (DCs) play a critical role in various immune responses involving $CD4^+$ T cells and have been used to generate anti-tumor immunity. Chemotherapy induces severe side effects including immunosuppression in patients with cancer. Although immunosuppression has been studied, the effects of anticancer drugs on DCs are not fully determined. In this study, we demonstrated that CD40 activation strongly protected DCs from 5-fluorouracil (5-FU) or mitomycin C-induced apoptosis. DCspecific surface markers, including CD11c and major histocompatibility complex (MHC) class II, were used for identifying DCs. CD 40 activation with anti-CD40 mAb significantly enhanced the viability of DCs treated with 5-FU or mitomycin C, assayed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Fluorescence staining and analysis clearly confirmed the enhancing effect of anti-CD40 mAb on the viability of DCs, suggesting that CD40 activation may transduce critical signals for the viability of DCs. Annexin V staining assay showed that CD40 significantly protected DCs from 5-FU or mitomycin C-induced apoptosis. Taken together, this study shows that CD40 activation with anti-CD40 mAb has strong anti-apoptosis effect on DCs, suggesting that CD40 activation may overcome the immunosuppression, especially downregulation of number and function of DCs in chemotherapy-treated cancer patients.

• Journal of Microbiology and Biotechnology
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• v.13 no.2
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• pp.196-201
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• 2003

The mixture (PM) of Saccharomyces cerevisiae and fermented rice bran on the activation of macrophage and bone marrow cell proliferation was studied in mice. PM stimulated not only the activation of macrophage (1.8-fold of saline) but also IL-6 production from macrophage (1.5-fold) at 2.0 g/㎏/day during 7 days of oral administration. By the culture supernatant of Peyer's patch cells from C3H/HeJ mice fed PM at 2.0 g/㎏/day for 7 days, the bone marrow cells significantly proliferated compared with that of mice receiving only saline (1.7-fold). In addition, the contents of GM-CSF and IL-6 in the culture supernatant of Peyer's patch cells from mice fed PM at 2.0 g/㎏/day were increased in comparison with those from the control (1.8 and 1.4-fold, respectively). These results revealed that oral administration of PM may modulate IL-6 production to induce the activation of macrophage, and also enhance secretion of hematopoietic growth factors such as GM-CSF and IL-6 from Peyer's patch cells.

• Toxicological Research
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• v.30 no.4
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• pp.277-282
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• 2014

To develop a composition for enhancing immunity, based on alcohol extracts of the bumblebee as an active ingredient, bumblebee ethanol extracts were evaluated for their protective effect in chronic models of inflammation, adjuvant induced rat arthritis. B. terrestris worker extract (SDIEX) and, B. hypocrita sapporoensis lava and pupa extract (SPDYBEX), significantly decreased paw edema in arthritic rats, at a dose 100 mg/kg, respectively. The cytokine levels related inflammation of COX-2, $sPLA_2$, VEGF, and TNF-${\alpha}$, were decreased, compared to positive control, indomethacin (5 mg/kg). Histopathological data demonstrated decreases inflammatory activity, hind paw edema, and repaired hyaline articular cartilage in DRG over a 2 wk administration. HPLC and GC-MS analysis of SDIEX and SPDYBEX revealed the presence of cantharidin.

• Food Science and Biotechnology
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• v.27 no.6
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• pp.1791-1799
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• 2018

In this study, the immunomodulatory activity of oligopeptide (CP) derived from solid-state fermented cottonseed meal were investigated in immunosuppressed BALB/c mice models by treatment with cyclophosphamide (CY). Results indicated that oligopeptide increased the thymus and spleen indices of CY-treated mice. The count of plague forming cells (PFC) and the content of half serum hemolysis ($HC_{50}$) in immunosuppressive mice were restored to the normal level in CP-10 and CP-20 groups while the cytokines interleukin (IL)-2, IL-6, and tumor necrosis factor alpha (TNF-${\alpha}$) were increased significantly in CP-20 group. Similar increasing the immunoglobulin of IgG and IgM content in the serum of CP-10 group were also observed. These findings indicated that oligopeptide derived from solid-state fermented cottonseed meal had a strong immune-enhancing activity as well as a protective effect against immunosuppression induced by cyclophosphamide in mice.

• BMB Reports
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• v.52 no.11
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• pp.635-640
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• 2019

CpG-DNA triggers the proliferation and differentiation of B cells which results in the increased production of antibodies. The presence of bacteria-reactive IgM in normal serum was reported; however, the relevance of CpG-DNA with the production of bacteria-reactive IgM has not been investigated. Here, we proved the function of CpG-DNA for the production of bacteria-reactive IgM. CpG-DNA administration led to increased production of bacteria-reactive IgM both in the peritoneal fluid and serum through TLR9 signaling pathway. When we stimulated B cells with CpG-DNA, production of bacteria-reactive IgM was reproduced in vitro. We established a bacteria-reactive monoclonal IgM antibody using CpG-DNA stimulated-peritoneal B cells. The monoclonal IgM antibody enhanced the phagocytic activity of RAW 264.7 cells against S. aureus MW2 infection. Therefore, we suggest that CpG-DNA enhances the antibacterial activity of the immune system by triggering the production of bacteria-reactive IgM. We also suggest the possible application of the antibodies for the treatment of antibiotics-resistant bacterial infections.

• 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.

• Journal of Yeungnam Medical Science
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• v.38 no.1
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• pp.27-33
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• 2021

The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.106-106
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• 2019

The leaves of Phaleria nisidai Kaneh. have been used as a beverage for tonic and immune-enhancing effect in Palau. Recently, extract of the plants showed anti-diabetic effect in clinical trial and possibility could be used as a medicine for diabetes. However, in vitro and in vivo experiments which elucidate cytotoxicity and biological mechanism have not been studied yet. To begin the series of in vitro and in vivo anti-diabetic studies, we evaluated cell viability of pancreatic beta cell lines to figure it out toxicity of the extract. The leaves of Phaleria nisidai were extracted with distilled water and 70% EtOH, and followed by evaporation and lyophilization. And, MIN6 and RIN-m5F cell lines were used for assessment of cell viability. MTT assay was adopted to evaluated a toxicity. Any of extract and concentration used in this study did not show cytotoxicity in the cell lines. Furthermore, morphological change was not observed. These results means Phaleria nisidai might be a medicinal resource when further biological and safety studies would be performed.

• Journal of Animal Reproduction and Biotechnology
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• v.36 no.4
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• pp.285-291
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• 2021

Mesenchymal stem cells (MSCs) have been recognized as a therapeutic tool for various diseases due to its unique ability for tissue regeneration and immune regulation. However, poor survival during in vitro expansion and after being administrated in vivo limits its clinical uses. Accordingly, protocols for enhancing cell survivability is critical for establishing an efficient cell therapy is needed. CDDO-Me is a synthetic C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, which is known to stimulate nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. Herein, report that CDDO-Me promoted the proliferation of MSCs and increased colony forming units (CFU) numbers. No alteration in differentiation into tri-lineage mesodermal cells was found after CDDO-Me treatment. We observed that CDDO-Me treatment reduced the cell death induced by oxidative stress, demonstrated by the augment in the expression of Nrf2-downstream genes. Lastly, CDDO-Me led to the nuclear translocation of NRF2. Our data indicate that CDDO-Me can enhance the functionality of MSCs by stimulating cell survival and increasing viability under oxidative stress.

• Mycobiology
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• v.50 no.1
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• pp.1-11
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• 2022

The ascomycete fungus Cordyceps militaris infects lepidopteran larvae and pupae and forms characteristic fruiting bodies. Owing to its immune-enhancing effects, the fungus has been used as a medicine. For industrial application, this fungus can be grown on geminated soybeans as an alternative protein source. In our study, we performed a comprehensive transcriptomic analysis to identify core gene sets during C. militaris cultivation on germinated soybeans. RNA-Seq technology was applied to the fungal cultures at seven-time points (2, 4, and 7-day and 2, 3, 5, 7-week old cultures) to investigate the global transcriptomic change. We conducted a time-series analysis using a two-step regression strategy and chose 1460 significant genes and assigned them into five clusters. Characterization of each cluster based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases revealed that transcription profiles changed after two weeks of incubation. Gene mapping of cordycepin biosynthesis and isoflavone modification pathways also confirmed that gene expression in the early stage of GSC cultivation is important for these metabolic pathways. Our transcriptomic analysis and selected genes provided a comprehensive molecular basis for the cultivation of C. militaris on germinated soybeans.