• Journal of Ginseng Research
• /
• v.45 no.3
• /
• pp.456-463
• /
• 2021

Background: Keratinocytes form a physical barrier and act as an innate immune cell in skin. Keratinocytes secrete pro-inflammatory cytokines, such as interleukin (IL)-1β, resulting from inflammasome activation when exposed to ultraviolet (UV) irradiation. Korean Red Ginseng extracts (RGE) have been well-studied as modulators of inflammasome activation in immune cells, such as macrophages. In the study, we elucidated the role of RGE on the UV-mediated inflammasome activation in keratinocytes compared with that in macrophages. Methods: Human skin keratinocyte cells (HaCaT), human epidermal keratinocytes (HEK), human monocyte-like cells (THP-1), and mouse macrophages were treated with RGE or a saponin fraction (SF) or non-saponin fraction (NS) of RGE before and after UV irradiation. The secretion levels of IL-1β, as an indicator of inflammasome activation, were analyzed. Results: The treatment of RGE or SF in macrophages after UV irradiation inhibited IL-1β secretion, but similar treatment in HaCaT cells did not. However, the treatment of RGE or SF in HaCaT cells in the presence of poly I:C, a toll-like receptor (TLR) 3 ligand, before UV exposure elicited the inhibition of the IL-1β secretion. The inhibition was caused by the disruption by RGE or SF of the TLR mediating up-regulation of the pro-IL-1β and NLRP3 genes during the priming step. Conclusion: RGE and its saponins inhibit IL-1β secretion in response to UV exposure in both keratinocytes and macrophages. In particular, RGE treatment interrupted only the priming step in keratinocytes, although it did attenuate both the priming and activation steps in macrophages.

• Microbiology and Biotechnology Letters
• /
• v.36 no.2
• /
• pp.135-141
• /
• 2008

Immunomodulating effect of Salicornia herbacea extract on the mouse splenocytes was investigated. Crude S. herbacea polysaccharide extract (CSP) and other kinds of fine S. herbacea polysaccharides (SPI and SPII) were prepared from S. herbacea by hot water extraction and further ultrafiltration and gel filtration chromatography. In vitro experiment, the mouse splenocytes and separated T cells were treated with CSP, SPI or SPII (0.5, 1, 2, 4 mg/ml). In vivo experiment, three different S. herbacea extracts were orally administrated everyday for one week. For the basic data, body weight and physiological parameters such as organ weight and spleen index were observed. The proliferation of the cells was used as an index for immunemodulating activity and the effect of proliferation was evaluated using MTS assay. The CSP, SPI and SPII directly induced the proliferation of splenocytes and separated T cells in a dose-dependent manner. In results, the proliferation was more increased in the SPI and SPII treated cells than in the CSP treated cells. The best proliferation was shown in the splenocytes cultured with SPI at the concentration of 4 mg/ml for 24 hr. The proliferation of splenocytes and separated T-cells was higher (3.2 and 3.5 times, respectively) than the control. Moreover, when the mouse splenocytes were treated with mitogen, the efficient proliferation was shown in the splenocytes cultured with SPI. In conclusion, polysaccharides from S. herbacea showed a substantial immunomodulating activity in the mouse immune cells.

• Toxicological Research
• /
• v.22 no.2
• /
• pp.95-102
• /
• 2006

Exposure to soluble nickel compound produces toxic effects on immune system, but the mechanism of action remains to be elucidated. Differential gene expression was studied to understand the potential molecular mechanism responsible for acute toxicity induced by nickel acetate in spleen cells. We exposed mouse spleen cells to nickel acetate with a nontoxic dose ($40{\mu}M$) and then extracted total RNA at 6 h and 12 h after exposure. The RNA was hybridized onto 10K mouse oligonucleotide microarrays, and data were analyzed using GeneSpring 7.1. Nickel had a modest effects on expression of many genes, in the range of 1.3-3 fold. The expression profile showed time-dependent changes in expression levels of differentially expressed genes, including some important genes related to cell cycle, apoptosis and DNA repair. In hierarchical cluster analysis of duplicate experiments, 111 genes were screened out. Out of these, 44 genes showing time- dependent up-regulation (>1.5 fold) and 38 genes showing down-regulation (>1.5 fold) at all time points were chosen for further analysis. The change in the expression of three genes (GPX1, GADD45B and FAIM) after nickel treatment was validated using RT-PCR. As a rule, a number of genes appear to be coordinately regulated between cell survival and cell death from nickel toxicity. In conclusion, changes in the gene profile in the spleen after nickel treatment are complex and genes with diverse functions are modulated. These findings will be contributed to the understanding of the complicated biological effects of nickel.

• Molecules and Cells
• /
• v.22 no.2
• /
• pp.189-197
• /
• 2006

Prolactin (PRL) is a pituitary hormone involved in various physiological processes, including lactation, mammary development, and immune function. To further investigate the in vivo and comparative endocrine roles of PRL, mouse PRL cDNA fused to the cytomegalovirus promoter, was introduced into muscle by direct injection. Previously we studied the function of rat PRL using the same protocol. PRL mRNA was detected in the muscle following injection by RT-PCR and subsequent Southern blot analysis. PRL was also detected and Western blot analysis revealed a relatively high level of serum PRL. In the pCMV-mPRL-injected female mice, the estrous cycle was extended, especially in diestrus stage and the uterus thickening that was shown in normal estrous stage was not observed. In the pCMV-mPRL-injected male mice, new blood vessels were first found at 5 weeks of age and fully developed blood vessels were found after 8 weeks in the testis. The number of Leydig cells increased within the testis and the testosterone level in serum was observed high. Finally, the number of white blood cells (WBCs) increased in the pCMV-mPRL-injected mice. The augmentation of WBCs persisted for at least 20 days after injection. When injection was combined with adrenalectomy, there was an even greater increase in number of WBCs, especially lymphocytes. This increase was returned normal by treatment with dexamethansone. Taken together, our data reveal that intramuscularly expressed mouse PRL influences reproductive functions in female, induces formation of new blood vessels in the testis, and augments WBC numbers. Of notice is that the Leydig cell proliferation with increased testosterone was conspicuously observed in the pCMV-mPRL-injected mice. These results also suggest subtle difference in function of PRL between mouse and rat species.

• Journal of Digital Convergence
• /
• v.13 no.1
• /
• pp.341-351
• /
• 2015

This study was aimed to evaluate the effects of Cypress oil(CS) on anti-asthmatic activities in a mouse model of allergic asthma. Using an Ovalbumin-induced allergic asthma mouse model, 0.3% of CS was administered to experimental group using a nebulizer for 3 weeks on a basis of 3 times per week and 30min each time. The degree of airway hypersensitivity, the number of eosinophil in white blood cells, the number of immune cells and the change of cytokine in lung tissue were evaluated. The degree of airway hypersensitivity, the number of eosinophil, IL-5 and IL-13 levels in lung tissue, IgE in serum, the number of CCR3, CD3, CD4 cells were significantly decreased in experimental group treated with CS. These results suggested that CS may have a positive effects on Th2 cytokine and eosinophils which are major factors of asthma responses. Therefore CS might be of therapeutic value in treating asthma.

• IMMUNE NETWORK
• /
• v.22 no.6
• /
• pp.49.1-49.15
• /
• 2022

Exosomes derived from mesenchymal stem cells (MSCs) could protect against myocardial infarction (MI). TLR4 is reported to play an important role in MI, while microRNA-182-5p (miR-182-5p) negatively regulates TLR4 expression. Therefore, we hypothesize that MSCs-derived exosomes overexpressing miR-182-5p may have beneficial effects on MI. We generated bone marrow mesenchymal stem cells (BM-MSCs) and overexpressed miR-182-5p in these cells for exosome isolation. H₂O₂-stimulated neonatal mouse ventricle myocytes (NMVMs) and MI mouse model were employed, which were subjected to exosome treatment. The expression of inflammatory factors, heart function, and TLR4 signaling pathway activation were monitored. It was found that miR-182-5p decreased TLR4 expression in BM-MSCs and NMVMs. Administration of exosomes overexpressing miR-182-5p to H₂O₂-stimulated NMVMs enhanced cell viability and suppressed the expression of inflammatory cytokines. In addition, they promoted heart function, suppressed inflammatory responses, and de-activated TLR4/NF-κB signaling pathway in MI mice. In conclusion, miR-182-5p transferred by the exosomes derived from BM-MSCs protected against MI-induced impairments by targeting TLR4.

• IMMUNE NETWORK
• /
• v.14 no.4
• /
• pp.219-225
• /
• 2014

We examined the immunogenicity of H-2 class I-restricted and HLA-A2-restricted epitopes through peptide immunization of HLA-A2-transgenic mice that also express mouse H-2 class I molecules. All four of the tested epitopes restricted by H-2 class I robustly elicited T-cell responses, but four of seven epitopes restricted by HLA-A2 did not induce T-cell responses, showing that HLA-A2-restricted peptide epitopes tend to be poorly immunogenic in HLA-A2-transgenic mice. This finding was confirmed in HLA-A2-transgenic mice infected with a recombinant vaccinia virus expressing hepatitis C virus proteins. We examined the precursor frequency of epitope-specific naïve $CD8^+$ T cells in HLA-A2-transgenic and conventional C57BL/6 mice and found that the poor immunogenicity of HLA-A2-restricted peptide epitopes is related to the paucity of naïve $CD8^+$ T-cell precursors in HLA-A2-transgenic mice. These results provide direction for the improvement of mouse models to study epitope repertoires and the immunodominance of human T-cell responses.

• Korean Journal of Acupuncture
• /
• v.28 no.3
• /
• pp.33-41
• /
• 2011

Objectives : The purpose of this study is to investigate effects of Scutellariae Radix water extract on hydrogen peroxide production in LPS-induced RAW 264.7 mouse macrophages. Methods : Scutellariae Radix produced from South Korea (SK) and Scutellariae Radix produced from China (SC) were extracted by hot water. Effects of SK and SC on hydrogen peroxide production in LPS-induced RAW 264.7 were measured by dihydrorhodamine 123 assay after 20, 24, 28, 44, 48, and 52 h incubation at the concentrations of 10, 25, 50, and 100 ug/mL. Results : SK significantly increased hydrogen peroxide production in LPS-induced RAW 264.7 cells for 20, 24, 28, 44, 48, and 52 h incubation at the concentrations of 10, 25, 50, and 100 ug/mL (P < 0.05). But SC did not represent any significant effect on hydrogen peroxide production in LPS-induced RAW 264.7 cells. Conclusions : These results suggest that Scutellariae Radix, especially produced from South Korea, has the immune-enhancing property related with its increasement of bacteriocidal hydrogen peroxide production in LPS-induced macrophages.

• Korean Journal of Oriental Medicine
• /
• v.14 no.3
• /
• pp.57-63
• /
• 2008

Glehnia littoralis (Umbelliferae) is the medicinal plant used traditionally for treatment of immune-related diseases. Prostaglandins and nitric oxide (NO) have been implicated as important mediators in the processes of inflammation and carcinogenesis. For understanding the mechanisms for pharmacological activities of Glehnia littoralis, we evaluated the inhibitory activity of Glehnia littoralis on lipopolysaccharide (LPS)-induced prostaglandin $E_2$ ($PGE_2$) and NO production in mouse macrophage RAW264.7 cells. The results showed that the extract of Glehnia littoralis inhibited LPS- induced $PGE_2$ production effectively, but not NO. Additional study revealed that the extract of Glehnia littoralis suppressed cyclooxygenase-2 (COX-2) expression in a dose-dependent manner. Present study suggests that Glehnia littoralis may have anti-inflammatory and/or cancer chemopreventive activity through the inhibition of $PGE_2$ production by the suppression of COX-2 activity.

• BMB Reports
• /
• v.54 no.9
• /
• pp.464-469
• /
• 2021

Cardiomyocyte differentiation occurs through complex and finely regulated processes including cardiac lineage commitment and maturation from pluripotent stem cells (PSCs). To gain some insight into the genome-wide characteristics of cardiac lineage commitment, we performed transcriptome analysis on both mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs) at specific stages of cardiomyocyte differentiation. Specifically, the gene expression profiles and the protein-protein interaction networks of the mESC-derived platelet-derived growth factor receptor-alpha (PDGFRα)⁺ cardiac lineage-committed cells (CLCs) and hiPSC-derived kinase insert domain receptor (KDR)⁺ and PDGFRα⁺ cardiac progenitor cells (CPCs) at cardiac lineage commitment were compared with those of mesodermal cells and differentiated cardiomyocytes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the genes significantly upregulated at cardiac lineage commitment were associated with responses to organic substances and external stimuli, extracellular and myocardial contractile components, receptor binding, gated channel activity, PI3K-AKT signaling, and cardiac hypertrophy and dilation pathways. Protein-protein interaction network analysis revealed that the expression levels of genes that regulate cardiac maturation, heart contraction, and calcium handling showed a consistent increase during cardiac differentiation; however, the expression levels of genes that regulate cell differentiation and multicellular organism development decreased at the cardiac maturation stage following lineage commitment. Additionally, we identified for the first time the protein-protein interaction network connecting cardiac development, the immune system, and metabolism during cardiac lineage commitment in both mESC-derived PDGFRα⁺ CLCs and hiPSC-derived KDR⁺PDGFRα⁺ CPCs. These findings shed light on the regulation of cardiac lineage commitment and the pathogenesis of cardiometabolic diseases.