• Animal Bioscience
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• v.37 no.7
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• pp.1141-1155
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• 2024

Objective: RNA epigenetic modifications play an important role in regulating immune response of mammals. Bovine mastitis induced by Staphylococcus aureus (S. aureus) is a threat to the health of dairy cattle. There are numerous RNA modifications, and how these modification-associated enzymes systematically coordinate their immunomodulatory effects during bovine mastitis is not well reported. Therefore, the role of common RNA modification-related genes (RMRGs) in bovine S. aureus mastitis was investigated in this study. Methods: In total, 80 RMRGs were selected for this study. Four public RNA-seq data sets about bovine S. aureus mastitis were collected and one additional RNA-seq data set was generated by this study. Firstly, quantitative trait locus (QTL) database, transcriptome-wide association studies (TWAS) database and differential expression analyses were employed to characterize the potential functions of selected enzyme genes in bovine S. aureus mastitis. Correlation analysis and weighted gene co-expression network analysis (WGCNA) were used to further investigate the relationships of RMRGs from different types at the mRNA expression level. Interference experiments targeting the m⁶ A demethylase FTO and utilizing public MeRIP-seq dataset from bovine Mac-T cells were used to investigate the potential interaction mechanisms among various RNA modifications. Results: Bovine QTL and TWAS database in cattle revealed associations between RMRGs and immune-related complex traits. S. aureus challenged and control groups were effectively distinguished by principal component analysis based on the expression of selected RMRGs. WGCNA and correlation analysis identified modules grouping different RMRGs, with highly correlated mRNA expression. The m⁶ A modification gene FTO showed significant effects on the expression of m⁶ A and other RMRGs (such as NSUN2, CPSF2, and METTLE), indicating complex co-expression relationships among different RNA modifications in the regulation of bovine S. aureus mastitis. Conclusion: RNA epigenetic modification genes play important immunoregulatory roles in bovine S. aureus mastitis, and there are extensive interactions of mRNA expression among different RMRGs. It is necessary to investigate the interactions between RNA modification genes regulating complex traits in the future.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.11
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• pp.1564-1570
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• 2016

The present study investigated the immunomodulatory effects of high-purity ${\beta}$-1.3/1.6-glucan on macrophages, natural killer (NK) cells, and T cell-mediated factors. Effect of high-purity ${\beta}$-1.3/1.6-glucan on cytotoxicity in macrophages was investigated. Using macrophages, cytotoxicity of high-purity ${\beta}$-1.3/1.6-glucan was evaluated by MTT assay. We treated high-purity ${\beta}$-1.3/1.6-glucan at concentrations of 10, 50, 100, 150, 200, and $250{\mu}g/mL$ in macrophages. High-purity ${\beta}$-1.3/1.6-glucan did not affect macrophage viability. Phagocytic activity was assessed using zymosan. Activity of high-purity ${\beta}$-1.3/1.6-glucan on macrophages significantly increased as compared with zymosan. We treated high-purity ${\beta}$-1.3/1.6-glucan to murine NK cells co-incubated with YAC-1 cells. High-purity ${\beta}$-1.3/1.6-glucan resulted in significantly increased activity of NK cells as compared with the control. In addition, treatment of macrophages with high-purity ${\beta}$-1.3/1.6-glucan resulted in significantly increased activity of T cell-mediated cytokine (IL-2, IL-12, $IFN-{\gamma}$, and $TNF-{\alpha}$) levels and CD4+/CD8+ T cells as compared with the control. In conclusion, high-purity ${\beta}$-1.3/1.6-glucan could enhance the immune response through activation of macrophages, NK cells, and T cell-mediated factors.

• Clinical and Experimental Pediatrics
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• v.51 no.8
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• pp.879-885
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• 2008

Purpose : The human lung fibroblast may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, which are important in airway remodeling. Vascular endothelial growth factor (VEGF) induces mucosal edema and angiogenesis. Thymus and activation regulated chemokine (TARC) induces selective migration of T helper 2 cells. We investigated whether human lung fibroblasts produced VEGF and TARC, and the effects were augmented with the co-culture of fibroblasts and human bronchial smooth muscle cells (HBSMC), and whether dexamethasone can inhibit the proliferation and the release of VEGF in lung fibroblasts. Methods : Human lung fibroblasts were cultured with and without HBSMC, growth-arrested in serum-deprived medium, and pretreated with dexamethasone for 16 hours. After 24-hour stimulation with platelet derived growth factor-BB (PDGF-BB) and/or transforming growth factor-${\beta}$ (TGF-${\beta}$), culture supernatant was harvested for assays of VEGF and TARC. Cell proliferation was assayed using BrdU cell proliferation ELISA kit. Results : 1) The release of VEGF was significantly increased after stimulation with TGF-${\beta}$, and its release was augmented when co-stimulated with PDGF and TGF-${\beta}$. 2) VEGF release induced by PDGF or TGF-${\beta}$ was inhibited by dexamethasone. 3) There was no synergistic effect on the release of VEGF when human lung fibroblasts were co-cultured with HBSMC. 4) Dexamethasone did not suppress human lung fibroblasts proliferations. 5) Neither TGF-${\beta}$ nor PDGF induced TARC release from lung fibroblasts. Conclusion : Human lung fibroblasts may modulate airway remodeling by release of VEGF, but they have no synergistic effects when co-cultured with HBSMC. Dexamethasone suppresses VEGF release, not proliferation of lung fibroblast.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.5
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• pp.723-731
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• 2008

Immunomodulatory feed additives might offer alternatives to antimicrobial growth promoters in pig production. This experiment was designed to determine the effects of dietary galacto-mannan-oligosaccharide (GMOS) and chitosan oligosaccharide (COS) supplementation on the immune response in early-weaned piglets. Forty 15-day-old piglets (Duroc$\times$Landrace$\times$Yorkshire) with an average live body weight of $5.6{\pm}0.51kg$ were weaned and randomly assigned to 4 treatment groups that were fed maize-soybean meal diets containing either basal, 110 mg/kg of lincomycin, 250 mg/kg of COS or 0.2% GMOS, respectively, over a 2-week period. Another six piglets of the same age were sacrificed on the same day at the beginning of the study for sampling, in order to obtain baseline values. Interleukin (IL)-1${\beta}$gene expression in peripheral blood monocytes, jejunal mucosa and lymph nodes, as well as serum levels of IL-1${\beta}$ IL-2 and IL-6, IgA, IgG, and IgM, were evaluated for 5 pigs from each group at 15 and 28 days of age. The results indicate that weaning stress resulted in decreases in serum antibody and cytokine levels. Dietary supplementation with GMOS or COS enhanced (p<0.05) IL-1${\beta}$gene expression in jejunal mucosa and lymph nodes, as well as serum levels of IL-1${\beta}$ IL-2, IL-6, IgA, IgG and IgM compared to supplementation with lincomycin. These findings suggest that GMOS or COS may enhance the cell-mediated immune response in early-weaned piglets by modulating the production of cytokines and antibodies, which shows that GMOS or COS have different effects than the antibiotic on animal growth and health.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.2
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• pp.174-180
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• 2016

In this study, the effects of fermented goat milk (F-GM) on immunological activity and physical strength were examined. Splenocytes obtained from mice administered with F-GM showed increased responsinveness to mitogens, concanavalin-A (ConA), and lipopolysaccharide (LPS). Treatment with F-GM also significantly augmented production of interleukin (IL)-2 and interferon (IFN)-${\gamma}$, but not IL-4 or IL-10 from ConA-stimulated splenocytes. The activity of F-GM administration to enhance production of IL-2 and IFN-${\gamma}$ was confirmed based on mRNA expression of these cytokines by reverse transcription polymerase chain reaction. After immunization with keyhole limpet hemocyanin (KLH, 20 mg/mouse), mice administered F-GM showed significantly higher antibody titers against KLH than those of phosphate-buffered saline-treated mice, and showed the highest titer 5 weeks after KLH immunization. Analysis for determining isotypes of antibodies revealed that administration of F-GM elicited KLH-specific antibody titers of IgG1, IgG2a, and IgM. In a delayed type hypersensitivity (DTH) test carried out 7 weeks after the primary immunization, F-GM-treated mice showed a higher DTH reaction than the control mice. Furthermore, the swimming test found that administration of F-GM significantly increased swimming time. These results suggest that administration of F-GM enhances not only immune responses against antigens but also physical strength.

• Korean Journal of Plant Resources
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• v.24 no.5
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• pp.557-563
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• 2011

Platycodon grandiflorum (Korean name, Doraji) has been widely used in traditional herbal medicine as an expectorant for pulmonary disease and a remedy for respiratory disorders in Asia. Here, we investigated the effects of BtOH extract saponin fraction of P. gradiflourm (PGS) on phagocytosis and anti-tumor activity with related cytokine productions in RAW264.7 macrophage cells. The results showed that PGS increased phagocytosis, anti-tumor activity, TNF-${\alpha}$ and nitric oxide (NO) production without direct tumor cell cytotoxicity. To further investigate whether NO is involved in anti-tumor and phagocytic activities of PGS, cells were co-treated with specific iNOS inhibitors, L-NIL (N6-(1-iminoethyl)-L-lysine, dihydrochloride), to block NO production. PGS decreased anti-tumor activity in L-NIL-treated cells, whereas phagocytic activity was not inhibited under the same conditions, indicating that the anti-tumor activity by PGS appears to be conducted by NO. These findings suggest that P. grandiflorum could be used a potential nutrition therapeutic agent for cancer patients.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.3
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• pp.307-313
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• 2015

The present study investigated the immunomodulatory effects of Curcuma longa L. ethanol extracts on natural killer (NK) cells and T cells. We treated Curcuma longa L. ethanol extracts at concentrations of 20, 50, 100, and $150{\mu}g/mL$ to murine NK cells co-incubated with YAC-1 cells. Curcuma longa L. ethanol extracts resulted in increased NK cell activity compared to the control group at all concentrations. In the groups treated with Curcuma longa L. ethanol extracts, CD69 and IFN-${\gamma}$ expression levels significantly increased compared to the control group at 100 and $150{\mu}g/mL$. In addition, Curcuma longa L. ethanol extracts induced significant elevation of CD8+ T cell numbers in a dose-dependent manner. However, Curcuma longa L. ethanol extracts also led to reduction of CD4+ T cell and MHCII numbers. The findings of this study suggest that Curcuma longa L. ethanol extracts could enhance the immune response through activation of NK and cytotoxic T cells due to a proliferative shift of antigen presentation from MHCII to MHCI, presumably.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.483-489
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• 2002

APA-01, which is an aqueous extract of five Chinese herbs, is a modified formula of Huoxiang-Zhengqi-San. The effect of new herb extract on immune response was investigated. The parameter examined to assess apparent immune response of APA-01 in mice included changes of body weight, relative weight of immune organs, cell proliferation and cytokine gene expression. The body weight and relative weight of immune organs were not significantly changed among the tested groups. In the spleen cell prolijeration assay, APA-01 increased the cell proliferation in a dose-dependent manner. Methotrexate (MTX), an agent of immune suppression, inhibited the spleen cell proliferation (IC/sub 50/: 800㎍/㎖). However, APA-01 significantly inhibited the suppression of mouse spleen cell proliferation. Therefore, it seems that APA-01 has a reducing effect of immune suppression. Immunomodulatory effect of APA-01 was further investigated using reverse transcription polymerase chain reaction (RT-PCR) in mouse spleen cells. In RT-PCR test, APA-01 enhanced the expression of cyclooxygenase-2 (COX-2) mRNA in a dose-dependent manner. In spite of immune suppression by MTX, COX-2 mRNA was induced by co-treatment with APA-01. These results suggest that APA-01 stimulates the proliferation of spleen cells, regulates the expression of COX-2 mRNA, and accelerates the recovery of inhibition of spleen cell proliferation induced by MTX, thus providing the immunological basis for clinical benefit of APA-01.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.48.1-48.21
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• 2023

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC^BMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC^BMP2 were associated with migration and growth. MSC^BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC^BMP2. MSC^BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3⁺CD25⁺ Treg of CD4⁺ cells were further increased in ALI mice treated with MSC^BMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC^BMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC^BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.

• Korean Journal of Food Science and Technology
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• v.40 no.5
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• pp.522-527
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• 2008

Low molecular peptides were isolated from Asterias amurensis via SDS-PAGE. The peptides were separated via consecutive gel filtration as five fractions (F1-F5) according to molecular weights, based on the results of MALDI-TOF MS analysis. The molecular weight of the most active peptide was estimated as 15,000 daltons. The peptide showed cytotoxicity on normal human fibroblast cells at levels as low as 20% when 1.0 mg/mL of the samples was added. The peptide also exhibited higher levels of nitric oxide production from macrophages than the lipopolysaccaharides. It was determined that prostaglendin $E_2$ production was significantly inhibited, up to 127.8% as compared to the control. The low molecular peptide inhibited hyaluronidase activity as 535.7 ${\mu}g/mL$ of $IC_{50}$. It can be concluded that the relatively low molecular weight peptide, fucoidan, from A. amurensis has excellent cosmetic and immunomodulatory activities, which can be considered as a possible resource of new cosmetic agents for skin immunomodulation.