• Journal of Microbiology and Biotechnology
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• v.29 no.11
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• pp.1739-1744
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• 2019

The present study evaluates the immunomodulatory effect of Bifidobacterium longum KACC 91563 in murine primary splenocytes and macrophages. B. longum KACC 91563 regulated T- and B-cell proliferation and inhibited the Th1 (IL-2, IFN-γ)/Th2 (IL-4, IL-10) cytokine imbalance and immune cytokine production. Moreover, immunoglobulin E (IgE) levels were significantly lower after treatment with B. longum KACC 91563. These findings suggest that B. longum KACC 91563 could modulate the systemic immune system toward both IgE production and regulation of the Th1/Th2 balance.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.908-912
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• 2005

Bio-Q is a modified prescription with the activities of supplementing Qi and blood in human body. In the present study, immunomodulatory effect of Bio-Q was examined. After oral administration of Bio-Q for 7 days to Balb/c mice, splenocytes were isolated and immunological experiments were performed. Bio-Q significantly increased the proliferation of splenocytes exposed to concanavalin A (Con A), while it did not in case of lipopolysaccharide (LPS) stimulation. Bio-Q also significantly increased CD3/CD19, CD4/CDB and NK cells by flow cytometric analysis. In addition, Bio-Q significantly enhanced the level of $INF-\gamma$ in splenocytes, but not $TNF-\alpha$ by ELISA. These results strongly suggest that Bio-Q has immunomodulatory activity through the regulation of T cell mediated immune pathway.

• Microbiology and Biotechnology Letters
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• v.44 no.3
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• pp.383-390
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• 2016

Mesenchymal stem cells (MSCs) are multipotent stem cells that can be differentiated into a variety of cell types, including adipocytes, osteoblasts, chondrocytes, β-pancreatic islet cells, and neuronal cells. MSCs have been reported to exhibit immunomodulatory effects in many diseases. Many studies have reported that MSCs have distinct roles in modulating inflammatory and immune responses by releasing bioactive molecules. Exosomes are cell-derived vesicles present in biological fluids, including the blood, urine, and cultured medium of cell cultures. In this study, we investigated the immunomodulatory effects of mouse adipose tissue-derived MSCs (mAD-MSCs), cultured medium (MSC-CM) of mAD-MSCs, and mAD-MSC-derived exosomes (MSC-Exo) on lipopolysaccharide (LPS)-induced RAW 264.7 cells. We observed that the expression levels of IL-1β, TNF-α, and IL-10 were significantly increased in LPS-stimulated RAW 264.7 cells compared to those in LPS-unstimulated RAW 264.7 cells. Additionally, these values were significantly (p < 0.05) decreased in mAD-MSCs-RAW 264.7 cell co-culture groups, MSC-CM-treated groups, and MSC-Exo-treated groups. MSCs can modulate the immune system in part by secreting cytokines and growth factors. We observed that immunomodulatory factors such as IL-1β, TNF-α, and IL-10 were secreted by mAD-MSCs under co-culturing conditions of mAD-MSCs with activated RAW 264.7 cells. In addition, mAD-MSC-derived exosomes exhibited similar immunomodulatory effects in activated RAW 264.7 cells. Therefore, our results suggest that mAD-MSCs have an immunomodulatory function through indirect contact.

• The Korean Journal of Food And Nutrition
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• v.30 no.6
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• pp.1140-1148
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• 2017

For the purpose of developing new immunomodulatory agents from broccoli, ethanol extract (BCEE), hot water extract (BCHW), and crude polysaccharide (BCCP) were isolated from broccoli, and their immunomodulatory activities and chemical properties were examined. In the in vitro cytotoxicity analysis, BCHW and BCCP did not affect the growth of tumor cells and normal cells. Murine peritoneal macrophages stimulated with BCCP showed higher production of IL-6, IL-12, and $TNF-{\alpha}$ cytokines than those stimulated with BCHW. Also, BCHW and BCCP did not show proliferation of splenic lymphocytes. In the in vitro assay for intestinal immunomodulatory activities, only BCCP enhanced GM-CSF secretion and the bone marrow cell-proliferating activity via cells in Peyer's patches at $1,000{\mu}g/mL$. Also, BCHW mainly contained 33.7% neutral sugars, such as arabinose, glucose, and galactose, and 30.7% uronic acid, and BCCP consisted of 42.6% neutral sugars, including arabinose, galactose, and glucose, and 50.5% uronic acid. The above results lead us to conclude that crude polysaccharide (BCCP) isolated from broccoli causes considerably high cytokine production in peritoneal macrophages and bone marrow cell proliferation, and the polysaccharide extraction process is indispensable for separation of new immunomodulatory agents from broccoli.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.298-306
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• 2017

Background: Compound K (CK) is a bioactive derivative of ginsenoside Rb1 in Panax ginseng (Korean ginseng). Its biological and pharmacological activities have been studied in various disease conditions, although its immunomodulatory role in innate immunity mediated by monocytes/macrophages has been poorly understood. In this study, we aimed to elucidate the regulatory role of CK on cellular events mediated by monocytes and macrophages in innate immune responses. Methods: The immunomodulatory role of CK was explored by various immunoassays including cell-cell adhesion, fibronectin adhesion, cell migration, phagocytic uptake, costimulatory molecules, reactive oxygen species production, luciferase activity, and by the measurement of mRNA levels of proinflammatory genes. Results: Compound K induced cell cluster formation through cell-cell adhesion, cell migration, and phagocytic activity, but it suppressed cell-tissue interactions in U937 and RAW264.7 cells. Compound K also upregulated the surface expression of the cell adhesion molecule cluster of differentiation (CD) 43 (CD43) and costimulatory molecules CD69, CD80, and CD86, but it downregulated the expression of monocyte differentiation marker CD82 in RAW264.7 cells. Moreover, CK induced the release of reactive oxygen species and induced messenger RNA expression of proinflammatory genes, inducible nitric oxide synthase, and tumor necrosis factor-alpha by enhancing the nuclear translocation and transcriptional activities of nuclear factor kappa-B and activator protein-1. Conclusion: Our results suggest that CK has an immunomodulatory role in innate immune responses through regulating various cellular events mediated by monocytes and macrophages.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.1
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• pp.48-55
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• 2019

Current studies have been reported that fruits such as berries may contain both antioxidant and antitumor polyphenols that may be important in this regard. We investigated the immunostimulatory effect of fermented blueberry (Vaccinium corymbosum L.) on cyclophosphamide-induced immunosuppression in animal model. Rats were administered blueberry yeast fermented powder (BYFP) at doses 30, 100, and 300 mg/kg for 4 weeks after cyclophosphamide (Cy) treatment, respectively. The immunomodulatory effect of BYFP were measured both in vitro and in vivo, and the changes of blood components were also analyzed. We found that BYFP recovered immunosuppression-mediated decreased liver, spleen, and thymus weights as well as up regulation of white blood cell, lymphocyte, and neutrophil in blood. Moreover, BYFP up-regulated IL-2, TNF-${\alpha}$, and IFN-${\gamma}$ pro-inflammatory cytokine production compared to immune suppressed control group, respectively. According to histological studies, BYFP regenerated significantly on Cy-mediated injured spleen at the high doses (BYFP 300) comparison with Cy-treated groups (immunosuppression). Collectively, these findings suggest that BYFP may have the potential as a dietary immunostimulatory agent.

• Journal of Pharmacopuncture
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• v.23 no.2
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• pp.62-70
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• 2020

Coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Currently, the management of patients with COVID-19 depends mainly on repurposed drugs which include chloroquine, hydroxychloroquine, lopinavir/ritonavir, ribavirin, remdesivir, favipiravir, umifenovir, interferon-α, interferon-β and others. In this review, the potential of Nigella sativa (black cumin seeds) to treat the patients with COVID-19 analyzed, as it has shown to possess antiviral, antioxidant, anti-inflammatory, anticoagulant, immunomodulatory, bronchodilatory, antihistaminic, antitussive, antipyretic and analgesic activities. Medline/PubMed Central/PubMed, Google Scholar, Science Direct, Directory of open access journals (DOAJ) and reference lists were searched to identify articles associated with antiviral and other properties of N.sativa related to the signs and symptoms of COVID-19. Various randomized controlled trials, pilot studies, case reports and in vitro and in vivo studies confirmed that N.sativa has antiviral, antioxidant, anti-inflammatory, immunomodulatory, bronchodilatory, antihistaminic, antitussive activities related to causative oraganism and signs and symptoms of COVID-19. N. sativa could be used as an adjuvant therapy along with repurposed conventional drugs to manage the patients with COVID-19.

• Journal of Ginseng Research
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• v.46 no.2
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• pp.304-314
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• 2022

Background: Ginsenosides are biologically active components of ginseng and have various functions. In this study, we investigated the immunomodulatory activity of a ginseng product generated from ginseng powder (GP) via enzymatic bioconversion. This product, General Bio compound K-10 mg solution (GBCK10S), exhibited increased levels of minor ginsenosides, including ginsenoside-F1, compound K, and compound Y. Methods: The immunomodulatory properties of GBCK10S were confirmed using mice and a human natural killer (NK) cell line. We monitored the expression of molecules involved in immune responses via enzyme-linked immunosorbent assay, flow cytometry, NK cell-targeted cell destruction, quantitative reverse-transcription real-time polymerase chain reaction, and Western blot analyses. Results: Oral administration of GBCK10S significantly increased serum immunoglobulin M levels and primed splenocytes to express pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ. Oral administration of GBCK10S also activated NK cells in mice. Furthermore, GBCK10S treatment stimulated a human NK cell line in vitro, thereby increasing granzyme B gene expression and activating STAT5. Conclusion: GBCK10S may have potent immunostimulatory properties and can activate immune responses mediated by B cells, Th1-type T cells, and NK cells.

• Journal of Microbiology and Biotechnology
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• v.30 no.3
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• pp.352-358
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• 2020

In this study we investigated the immune effects of oral administration of anionic macromolecules extracted from Codium fragile (CFAM) and red ginseng extract mixture on the peritoneal macrophage cells in immune-suppressed mice. Cyclophosphamide (CY) induces the immune-suppressed condition. CY-treated mice were orally fed with different concentrations of CFAM supplemented with red ginseng extract and the peritoneal macrophages collected. CY treatment significantly decreased the immune activities of peritoneal macrophages, compared to the normal mice. The administration of CFAM mixed with red ginseng extract significantly boosted the viability of macrophage cells and nitric oxide production of peritoneal macrophages. Further, the oral administration of CFAM mixed with red ginseng extract up-regulated the expression of iNOS, COX-2, and TLR-4 as well as cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ more than the red ginseng-treated group. This study showed that CFAM enhanced the immune activity of red ginseng extract in the peritoneal macrophage cells of immune-suppressed mice. Furthermore, CFAM might be used as a co-stimulant of red ginseng extract through the regulation of macrophage cells for the enhancement of human health and immunity.

• YAKHAK HOEJI
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• v.51 no.1
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• pp.35-43
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• 2007

To investigate the immunomodulatory roles of cyclic AMP (CAMP) on macrophage- and T lymphocyte-mediated immune responses, CAMP elevating agents were employed and carefully re-examined under the activation conditions of the cells. Various inhibitors tested dose-dependently blocked tumor necrosis factor (TNF)-${\alpha}$ production with IC$_{50}$ values ranged from 0.04 to 300 ${\mu}$M. Of the inhibitors, cAMP-elevating agents showed lower cytotoxicity assessed by lactate dehydrogenase (LDH) release, suggesting less toxic and more selective. In particular co-treatment of dbcAMP with a protein kinase C inhibitor staurosporine displayed the synergistic inhibition of TNF-${\alpha}$ production. The modulatory effect of dbcAMP on TNF-${\alpha}$ and nitric oxide (NO) was significantly affected by treatment time of dbcAMP. Thus, post-treatment of dbcAMP (three hours before LPS) abrogated dbcAMP's inhibitory activity and rather enhanced TNF-${\alpha}$ level up to 60%. In contrast, additional NO production was shown at the co-treatment of dbcAMP with LPS. Unlike simultaneous treatment of phorbol 12-myristate 13-acetate (PMA) and interferon (IFN)-${\gamma}$co-treatment, the combination of dbcAMP with other NO-inducing stimuli did not show drastic overproduction of NO. cAMP elevating agents also diminished splenocyte proliferation stimulated by concanavalin (Con) A, phytohemaglutinin A (PHA) and lipopolysaccharide (LPS). In addition, dbcAMP but not rolipram strongly suppressed CD8$^+$ T cells (CTLL-2). Finally, cAMP elevating agents were differentially involved in regulating CD98-mediated cell-cell adhesion. Thus, dbcAMP and rolipram significantly enhanced the cell-cell adhesion, whereas forskolin blocked. Therefore, our results suggest that CAMP elevating agents participate in various immune responses mediated by macrophages and T cells with a different fashion depending on cellular environments and activation signals.