• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2003.11a
• /
• pp.98-98
• /
• 2003

${\beta}$-(1,3)-D-Glucans have been known to exhibit antitumor and antimicrobial activities. The presence of dectin-1,${\alpha}$, ${\beta}$-glucan receptor of dendritic cell, on macrophage has been controvertial. RT-PCR analysis led to the detection of dectin-1${\alpha}$ and ${\beta}$ in murine macrophage Raw264.7 cell line. Among the various organs of mouse, dectin-1${\alpha}$ and ${\beta}$ were detected in the thymus, lung, spleen, stomach and intestine. To analyze gene expression modulated by ${\beta}$-glucan treated murine Raw264.7 macrophage, total mRNA was applied to cDNA microarray to interrogate the expression of 7,000 known genes. cDNA chip analysis showed that ${\beta}$-glucan of P. osteatus increased gene expressions of immunomodulating genes, membrane antigenic proteins, chemokine ligands, complements, cytokines, various kinases, lectin associated genes and oncogenes in Raw 264.7 cell line. When treated with ${\beta}$-glucan of P. osteatus and LPS, induction of gene expression of TNF-${\alpha}$ and IFN-R1 was confirmed by RT-PCR analysis. Induction of TNF-R type II expression was confirmed by FACS analysis. IL-6 expression was abolished by EDTA in ${\beta}$-glucan and LPS treated Raw264.7 cell line, indicating that ${\beta}$-glucan binds to dectin-l in a Ca$\^$＋＋/ -dependent manner. To increase antitumor efficacy of ${\beta}$-glucan, ginsenoside Rh2 (GRh2) was co-treated with ${\beta}$-glucan in vivo and in vitro tests. IC$\sub$50/ values of GRh2 were 20 and 25 $\mu\textrm{g}$/$m\ell$ in SNU-1 and B16 melanoma F10 cell line, respectively. Co-treatment with ${\beta}$-glucan and GRh2 showed synergistic antitumor activity with cisplatin and mitomycin C both in vitro and in vivo. Single or co-treatment with ${\beta}$-glucan and GRh2 increased tumor bearing mouse life span. Co-treatment with ${\beta}$-glucan and GRh2 showed more increased life span with mitomycin C than that with cisplatin. Antitumor activities were 67% and 72 % by co-injection with ${\beta}$-glucan and GRh2 in the absence or presence of mitomycin C, respectively.

• Asian-Australasian Journal of Animal Sciences
• /
• v.33 no.9
• /
• pp.1507-1519
• /
• 2020

Objective: The current research was aimed to profile the transcriptomic picture of the peripheral blood lymphocytes (PBLs) associated with immunity in Chinese Holsteins supplemented orally with coated folic acid during the periparturient period. Methods: The total of 123 perinatal cows were selected for this study and divided into three groups; group A (n = 41, 240 mg/500 kg cow/d), group B (n = 40, 120 mg/500 kg cow/d) and group C (n = 42, 0 mg/cow/d) based on the quantity of folic acid fed. Three samples of PBLs were selected from each folic acid treated group (high, low, and control) and RNA sequencing method was carried out for transcriptomic analysis. Results: The analysis revealed that a higher number of genes and pathways were regulated in response to high and low folic acid supplementation compared to the controls. We reported the novel pathways tumor necrosis factor (TNF) signaling, antigen processing and presentation, Staphylococcus aureus infection and nuclear factor (NF)-kappa B signaling pathways) and the key genes (e.g. C-X-C motif chemokine ligand 10, TNF receptor superfamily member 1A, cluster difference 4, major histocompatibility complex, class II, DQ beta, NF-kappa-B inhibitor alpha, and TNF superfamily 13) having great importance in immunity and anti-inflammation in the periparturient cows in response to coated folic acid treatment. Conclusion: Collectively, our study profiled first-time transcriptomic analysis of bovine lymphocytes and compared the involved cytokines, genes, and pathways between high vs control and low vs control. Our data suggest that the low folic acid supplementation (120 mg/500 kg) could be a good choice to boost appropriate immunity and anti-inflammation as well as might being applied to the health improvement of perinatal dairy cows.

• Korean Journal of Clinical Laboratory Science
• /
• v.50 no.2
• /
• pp.177-182
• /
• 2018

This study examined the effects of zerumbone on monocyte migration. Monocytes are recognized as important mediators of various inflammatory diseases, and the possibility of controlling inflammatory diseases by regulating the monocyte functions, such as activity and mobility, has been reported. MCP-1, which is a chemokine with levels that increase upon inflammation, causes the migration of the monocyte cell line, THP-1. Migration occurred at a concentration of 10 ng/mL MCP-1, and the highest migration occurred at 100 ng/mL and 200 ng/mL. MCP-1-induced THP-1 migration decreased by more than 40% in the presence of zerumbone. The concentration of cAMP, an important secondary messenger of the CCR2 signaling pathway, the MCP-1 receptor, was increased in the culture medium after a zerumbone treatment. The concentrations of cAMP decreased significantly under the MCP-1 treatment condition only. On the other hand, an increase in cAMP was observed when zerumbone and MCP-1 were treated simultaneously. Erk phosphorylation induced by an MCP-1 treatment was also found to decrease with the zerumbone treatment. This study introduces the possibility of controlling inflammatory diseases through the function of zerumbone, which regulates the migration of monocytes.

• Korean Journal of Poultry Science
• /
• v.47 no.1
• /
• pp.49-59
• /
• 2020

The present study determined the effect of dietary cultivated microalgae (Parachlorella sp.) on the growth and immune responses of pre-starter broilers. A total of 320 one-day-old birds (Ross 308) were allocated to 4 treatments with 8 blocks in a randomized complete block design. The four experimental diets consisted of a corn-soybean meal-based control diet, and three diets contained 0.5%, 1.0%, and 1.5% microalgae powder at the expense of cornstarch in the control diet. After feeding the experimental diets for 7 days, the body weight and feed intake of all birds were measured, and 8 birds were randomly selected from each treatment. Peripheral blood mononuclear cells (PBMCs) and serum were harvested for immune profile assessment, including cytokines and cell migration receptors. No differences in growth performance were observed among the treatments. The birds that were fed diets containing graded levels of microalga showed a linear increase in the mRNA expression of cytokine genes in PBMCs, including that of IL2, IL1β, and IL18 (P<0.05). With respect to the chemokine receptor genes in PBMCs, mRNA expression of CCR2, CCR9, and ITGA4 changed quadratically (P<0.05), but that of CCR7 increased linearly (P<0.01). Cytokine protein secretion in blood, including that of IL-1β and IL-6, increased linearly (P<0.01) with an increase in the microalgal content. Overall, the present results show that the indigenous microalgae powder used in this study could stimulate immunity with no detrimental effects on the growth performance of pre-starter broiler chickens.

• The Journal of the Korean bone and joint tumor society
• /
• v.18 no.1
• /
• pp.20-27
• /
• 2012

Purpose: The chemokine receptor CXCR4 has been reported to be aberrantly expressed in human cancer and has been shown to participate in cancer metastasis. We compared the expression of CXCR4 in conventional high-grade and low-grade central osteosarcomas, and determined if an association between CXCR4 expression and prognosis could be made. Materials and Methods: We performed the immunohistochemistry for CXCR4 in a total of 63 patients with osteosarcoma and determined the relationships according to the clinicopathologic variables and overall survival rates. Results: CXCR4 was detected in 76.3% of conventional high-grade osteosarcoma patients and in 36% of low-grade central osteosarcomas. Diffuse expression was noted in 47.4% of the high-grade osteosarcomas and all low-grade cases were focal positive. CXCR4 expression was significantly correlated with histologic grade (p<0.0001). While overall survival rate was reduced significantly with increased CXCR4 expression (p=0.0058), higher histologic grade (p<0.0001), and younger age (p=0.0140), survival rate did not correlate with gender, tumor size, or AJCC stage. Conclusion: Our results suggest that CXCR4 expression is associated with higher-grade tumors and with poor prognosis for osteosarcoma patients.

• Molecules and Cells
• /
• v.40 no.7
• /
• pp.476-484
• /
• 2017

C-X-C chemokine receptor 4 (CXCR4) stimulates cancer metastasis. NF-${\kappa}B$ regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-${\kappa}B$ promotes its transcriptional activity. Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-${\kappa}B$ in lung metastasis of cervical cancer. We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-${\kappa}B$ p65 (p65) and CXCR4 in cervical cancer cells. Knockdown of OGT inhibited the O-GlcNAcylation of p65 and decreased CXCR4 expression levels in HeLa cells. Thiamet G treatment increased O-GlcNAcylated p65, which subsequently enhanced CXCR4 expression levels. Inhibition of O-GlcNAcylation by 6-Diazo-5-oxo-L-norleucine (DON) treatment decreased p65 activation, eventually inhibiting CXCR4 expression in HeLa cells. Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). In addition, lung tissues from mice engrafted with shOGT cells exhibited lower p65 and CXCR4 immunoreactivity compared to tissues from mice engrafted with shCTL cells. Taken together, our data suggest that p65 O-GlcNAcylation promotes lung metastasis of cervical cancer cells by activating CXCR4 expression.

• The Korean Journal of Physiology and Pharmacology
• /
• v.23 no.5
• /
• pp.367-379
• /
• 2019

Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.

• Animal Bioscience
• /
• v.34 no.2
• /
• pp.276-284
• /
• 2021

Objective: The objective of this study was to determine whether a dietary vitamin E (VE) supplement could alleviate any detrimental effects of aged corn on lipid metabolism and antioxidant status in laying hens. Methods: The experiment consisted of a 2×3 factorial design with two corn types (normal corn and aged corn (stored for 4 yr) and three concentrations of VE (0, 20, and 100 IU/kg). A total of 216 Lohmann laying hens (50 wk of age) were randomly allocated into six treatment diets for 12 wk. Each treatment had 6 replicates of 6 hens per replicate. Results: The results show that aged corn significantly decreased the content of low-density lipoprotein cholesterol (p<0.05), and reduced chemokine-like receptor 1 (CMKLR1) mRNA expression (p<0.05) in the liver compared to controls. Diet with VE did not alter the content of crude fat and cholesterol (p>0.05), or acetyl-CoA carboxylase, lipoprotein lipase, fatty acid synthase or CMKLR1 mRNA expression (p>0.05) in the liver among treatment groups. Aged corn significantly increased the content of malondialdehyde (MDA) (p<0.05) and decreased superoxide dismutase (SOD) activity (p<0.05) in the liver. The VE increased the content of MDA (p<0.05) but decreased glutathione peroxidase (GSH-Px) activity in serum (p<0.01) and in the ovaries (p<0.05). Adding VE at 20 and 100 IU/kg significantly increased GSH-Px activity (p<0.05) in liver and in serum (p<0.01), 100 IU/kg VE significantly increased SOD activity (p<0.05) in serum. Aged corn had no significant effects on GSH-Px mRNA or SOD mRNA expression (p<0.01) in the liver and ovaries. Addition of 100 IU/kg VE could significantly increase SOD mRNA expression (p<0.01) in the liver and ovary. Conclusion: Aged corn affected lipid metabolism and decreased the antioxidant function of laying hens. Dietary VE supplementation was unable to counteract the negative effects of aged corn on lipid metabolism. However, addition of 100 IU/kg VE prevented aged corninduced lipid peroxidation in the organs of laying hens.

• The Journal of Korean Medicine
• /
• v.44 no.2
• /
• pp.106-118
• /
• 2023

Objectives: Network pharmacology is a method of constructing and analyzing a drug-compound-target network to predict potential efficacy and mechanisms related to drug targets. In that large-scale analysis can be performed in a short time, it is considered a suitable tool to explore the function and role of herbal medicine. Thus, we investigated the potential functions and pathways of Chongmyunggongjin-dan (CMGJD) on Alzheimer's disease (AD) via network pharmacology analysis. Methods: Using public databases and PubChem database, compounds of CMGJD and their target genes were collected. The putative target genes of CMGJD and known target genes of AD were compared and found the correlation. Then, the network was constructed using Cytoscape 3.9.1. and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results: The result showed that total 104 compounds and 1157 related genes were gathered from CMGJD. The network consisted of 1157nodes and 10034 edges. 859 genes were interacted with AD gene set, suggesting that the effects of CMGJD are closely related to AD. Target genes of CMGJD are considerably associated with various pathways including 'Positive regulation of chemokine production', 'Cellular response to toxic substance', 'Arachidonic acid metabolic process', 'PI3K-Akt signaling pathway', 'Metabolic pathways', 'IL-17 signaling pathway' and 'Neuroactive ligand-receptor interaction'. Conclusion: Through a network pharmacological method, CMGJD was predicted to have high relevance with AD by regulating inflammation. This study could be used as a basis for effects of CMGJD on AD.

• IMMUNE NETWORK
• /
• v.22 no.2
• /
• pp.16.1-16.20
• /
• 2022

The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against Listeria monocytogenes (LM). Fasting induced an increased number of CD103⁺CD11b^- DCs in both small intestinal lamina propria (SILP) and mesenteric lymph nodes (mLN). The SILP CD103⁺CD11b^- DCs showed proliferation and migration, coincident with increased levels of GM-CSF and C-C chemokine receptor type 7, respectively. At 24 h post-infection with LM, there was a significant reduction in the bacterial burden in the spleen, liver, and mLN of the short-term-fasted mice compared to those fed ad libitum. Also, short-term-fasted mice showed increased survival after LM infection compared with ad libitum-fed mice. It could be that significantly high TGF-β2 and Aldh1a2 expression in CD103⁺CD11b^- DCs in mice infected with LM might affect to increase of Foxp3⁺ regulatory T cells. Changes of major subset of DCs from CD103⁺ to CD103^- may induce the increase of IFN-γ-producing cells with forming Th1-biased environment. Therefore, the short-term fasting affects protection against LM infection by changing major subset of intestinal DCs from tolerogenic to Th1 immunogenic.