• Journal of Life Science
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• v.28 no.1
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• pp.17-25
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• 2018

In this study, we examined the efficacy of the immune regulation of ${\beta}$-1,3/1,6-glucan and Lactobacillus plantarum LM1004 on atopic dermatitis models. The oral administration of ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 on mice significantly decreased the amount of scratching, leakage to evans blue, and concentrations of serum immunoglobulin E (IgE) and histamine compared with the atopic dermatitis - induced group. When atopic dermatitis was induced, the transcription factors (GATA-3, retinoic acid-related orphan receptor ${\gamma}$ T [$ROR{\gamma}T$]) and cytokines (interleukin-4 [IL-4], IL-17) of Th2 and Th17 cells were overexpressed at the transcriptional level, and they significantly decreased with oral administration of ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004. In addition, ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 were shown to modulate the immune balance by increasing the expression of Th1 and Treg transcription (T-bet, forkhead box p3 [Foxp3]) and cytokines (interferon-${\gamma}$ [IFN-${\gamma}$], transforming growth factor-${\beta}$ [TGF-${\beta}$]). Galectin-9 and filaggrin were significantly lower in the atopic dermatitis - induced group and significantly higher in the ${\beta}$-1,3/1,6-glucan-treated group. In contrast, thymic stromal lymphopoietin (TSLP) was highest in the atopic dermatitis-induced group, while mice that were orally administered ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 showed similar TSLP levels to the control group. These results indicate that ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 have immunomodulatory effects and atopic dermatitis improvement effects in an animal model of atopic dermatitis. Therefore, it is expected that ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 can be used as natural materials in the treatment of atopic dermatitis.

• Korean Journal of Plant Resources
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• v.34 no.1
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• pp.23-30
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• 2021

Hemistepta lyrata Bunge (HL) has been used as a folk remedy to treat cancer, inflammation, bleeding, hemorrhoids and fever, and leaves and young shoots have been used as famine food. Nevertheless, the biological activities and underlying mechanisms of the anti-inflammatory effects remain unclear. In this study, it was undertaken to explore the functions of the aerial part of HL as a suppressor of inflammation by using RAW 264.7 cells. As immune response parameters, the productions of as nitric oxide (NO) and prostaglandin E2 (PGE2), cytokines such tumor necrotic factor (TNF)-α and interleukin (IL)-6 were evaluated. Although the release of TNF-α remained unchanged in HL-treated RAW 264.7 cells, the productions of NO, PGE2 and IL-6 were significantly increased at concentrations with no cytotoxicity. Furthermore, HL significantly attenuated the mitogen-activated protein kinases (MAPK) pathway including decreasing the phosphorylation of the extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein kinases. Collectively, this study provides evidence that HL inhibits the production of major pro-inflammatory molecules in LPS-stimulated RAW 264.7 cells via suppression of ERK and P38 MAPK signaling pathways. These findings suggest that the beneficial therapeutic effects of HL may be attributed partly to its ability to modulate immune functions in macrophages.

• Journal of Nutrition and Health
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• v.48 no.1
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• pp.9-18
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• 2015

Purpose: Poncirus trifoliata has been reported to have anti-inflammatory, antioxidant, and immune activities. However, its anti-obesity activity and the mechanism by which the water extract of dried, immature fruit of Poncirus trifoliata (PF-W) acts are not clear. This study suggests a potential mechanism associated with the anti-obesity activity of PF-W. Methods: We measured the effect of PF-W on lipoprotein lipase (LPL) regulation using enzyme-linked immunosorbent assay (ELISA) and an activity assay. The LPL regulation mechanism was examined by reverse transcription polymerase chain reaction (RT-PCR) to measure the mRNA expression of biomarkers related to protein transport and by western blot for analysis of the protein expression of the transcription factor CCAAT-enhancer-binding protein ($C/EBP{\beta}$). Results: The total polyphenol and flavonoid content of PF-W was $52.15{\pm}4.02$ and $6.56{\pm}0.47mg/g$, respectively. PF-W treatment decreased LPL content in media to $58{\pm}5%$ of that in control adipocyte media, and increased LPL content to $117{\pm}3.5%$ of that in control adipocytes, but did not affect the mRNA expression of LPL. PF-W also increased the mRNA expression of sortilin-related receptor (SorLA), a receptor that induces endocytosis and intracellular trafficking of LPL, in a concentration- and time-dependent manner. Finally, cell fractionation revealed that PF-W treatment induced the expression of $C/EBP{\beta}$, a SorLA transcription factor, in the nuclei of 3T3-L1 adipocytes. Conclusion: The LPL secretion and activity assay showed PF-W to be an LPL secretion inhibitor, and these results suggest the potential mechanism of PF-W involving inhibition of LPL secretion through $C/EBP{\beta}$-mediated induction of SorLA expression.

• Clinical and Experimental Reproductive Medicine
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• v.33 no.1
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• pp.45-52
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• 2006

Objective: Our purpose was to investigate the relationship between the levels of IL-6 and tumor necrosis factor-${\alpha}$ in the peritoneal fluid of women with and without endometriosis and infertile women. Methods: This study is prospective and case-control study in University hospital, enrolled thirty-four women with laparoscopic findings of minimal to severe endometriosis, and thirty-seven women with no visual evidence of pelvic endometriosis and with benign gynecologic disease. IL-6 and tumor necrosis factor-${\alpha}$ levels in peritoneal fluid were determined using commercial ELISA. IL-6 and tumor necrosis factor-${\alpha}$ concentrations were compared among women with and without endometriosis, and with infertile and fertile women, and then also compared according the revised American Fertility Society classification. Results: IL-6 and tumor necrosis factor-${\alpha}$ concentrations were higher than in the peritoneal fluid of women with endometriosis than in matched normal controls. Cyclic variations in IL-6 concentrations were seen in peritoneal fluid from patients with endometriosis: the concentrations in the secretory phase were significantly higher than those in the proliferative phase. The concentrations were higher than among of infertile women than in fertile women. A significant correlation between IL-6 and tumor necrosis factor-${\alpha}$ concentrations and endometriosis stage III and IV was noted. Conclusion: Increased levels of IL-6 and tumor necrosis factor-${\alpha}$ in patients with endometriosis in the peritoneal fluid may be relate to the pathogenesis of endometriosis suggesting that partially contribute to the disturbed immune regulation observed in patients with endometriosis.

• Biomedical Science Letters
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• v.4 no.1
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• pp.11-25
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• 1998

The HLA genes located in the short arm of chromosome 6 specify heterodimeric glycoproteins involved in the regulation of the immune response. Recently, in the elucidation of HLA polymorphism, serological and cellular typing methods have been replaced by DNA typing using polymerase chain reaction (PCR). The purpose of this study was to establish the HLA DNA typing methods and determine gene frequencies of HLA molecules in Koreans. PCR-SSP (sequence specific primers) and PCR-RFLP (restriction fragment length polymorphism) techniques were used for the analysis of HLA-A, -B, -C, DRBl genes and HLA-DQAl, DQBl, DPBl genes, respectively. The results of B-lymphoblastoid cells used for control experiment were consistent with the previous data identified in the 11th International Histocompatibility Workshop. Seventeen, 23, 16, 8, 16, 13 and 37 types of HLA-A, B, C, DQAl, DQBl, DPBl and DRBl alleles were found, respectively, in a total of unrelated 120 Korean individuals. The most frequent HLA alleles were $A^*$02 (27.0%), B$^*$40 (17.6%), Cw$^*$01 (19.2%), DQAl$^*$0301 (32.1%), DQBl$^*$0303 (12.9%), DPBl$^*$0501 (31.3%) and DRBl$^*$1501 (9.2%) among Koreans. This study shows that DNA typing method using PCR technique is a relatively simple, fast and practical tool for the determination of the HLA-class I and II genes. Moreover, the data of HLA gene frequencies could be useful for the Korean database before clinical applications, including organ and unrelated bone marrow transplantation, anthropological study, disease association and individual identification.

• The korean journal of orthodontics
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• v.29 no.1 s.72
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• pp.73-81
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• 1999

Midpalatal suture expansion is often used for patients haying narrow maxillary arch, cleft palate, respiratory handicap with narrow nasal cavity. CGRP has been known as a modulator of pain transmission in central nervous system and a local effector to peripheral tissue causing vasodilation, increase of blood flow, modulation of immune system, regulation of macrophagic function and stimulation of bone formation. To investigate changes of CGRP-immunoreactive nerve fibers in midpalatal suture during the expansion, immunohistochemical study was performed by using rats. Experimental rats (10 weeks, 250 gm) were divided into five groups (control, 1, 4, 7, 14 days group (each n=4) and applied orthodontic force (approximately 200gm) to upper anterior incisors. Frozen sections of midpalatal suture area were immunostained by using rabbit antisera. The results were as follows. ${\cdot}$ The CGRP-immunoreactive nerve fibers were hardly observed in control group. ${\cdot}$ In 1 day group, the CGRP-immunoreactive nerve fibers were more increased around the vessels than control group. ${\cdot}$ In 4 days group, the CGRP-immunoreactive nerve fibers were more increased than control group, but not more increased than 1 day group. Vascular diameter was more enlarged. ${\cdot}$ In 7 days group, especially, hematoxilin affinity of cells was remarkable and cells were arranged along the bone margin. The CGRP-immunoreactive nerve fibers were more reduced than 4 days group and vascular diameter was also reduced. ${\cdot}$ In 14 days group, the CGRP-immunoreactive nerve fibers were similar to those of 7 days group and the irregularity of bone margin was almost recoverd. In Conclusion, the CGRP-immunoreactive nerve fibers nay be related to initial neurogenic inflammatory reaction in expanding mid-palatal suture.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.6 no.1
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• pp.81-97
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• 2000

Objectives: This experimental study was carried out to evaluate the effects of aqueous and methanol extracts of Hedyotis diffusa which has long been used for cancer treatment in oriental medicines on the induction of apoptotic cell death in human lymphoid leukemia cell line, HL-60. Methods: Cells were treated with various concentrations (200 to $0.4{\mu}g$) and periods (6 to 30 hr) of $H_2O$ and methanol extracts of Hedyotis diffusa. Then, cells were tested for viability by MTT assay. Cells wrere treated with $200{\mu}g/ml$ of methanol extract fork various periods. Genomic DNA was isolated, separated, on 1.5% agarose gels, stained with ethidium bromide and visualized under UV light. Cells were treated with $200{\mu}g/ml$ of each extract for 16 hr. Then, cells were treated with Hoechst dye 33342 and observed by fluorescence microscopy. Cells were treated with various doses of each for 12 hr and $100{\mu}g/ml$ of methanol extract for various periods. Lysate from the cells used to measure the activity of Caspase-1 and-3 proteases by using fluorogenic peptide substrates including acetyl-YVAD-AMC and acetyl-DEVD-AMC, respectively. Cells were treated with $200{\mu}g/ml$ of each extract for various periods. Cell lysates were immunoprecipated with anti-JNKl antibodies. The immune complex was reacted with $32^p-ATP$ and c-Jun as a substrate. The phosphotransferase activity of JNKI was measured by using PhosphoImage analyzer (Fuji Co., Japan). Nuclear extracts were isolated and incubated with oligonucleotide probe of $NF-{\kappa}B$. Transcriptional activation of ${\kappa}B$ was measured by using EMSA and visualized by PhosphoImage analyzer (Fuji Co, Japan). Cell lysates were prepared and analyzed by Western blotting with anti-Bc12 antibodies and anti-Bax antibodies. Cells were pretreated with various doses of methanol extract for 2 hr. Then, the extract was removed by centrifugation. Cells were resuspended with RPMI-1640 media containing 0.3% agarose, 10% FBS, overlayred onto bottom layer agarose and incubated at $CO_2$ incubator for 6 days. The number of colony was counted under light microscopy ($\time100$). Results: The death of HL-60 cells was markedly induced by the addition of methanol extract of Hedyotis diffusa in a dose and time-dependent manners. The apoptotic characteristic ladder pattern of DNA strand break was observed in death of HL-60 cells. In addition, it was shown nucleus chromatin condensation and fragmentation under Hoechst staining. Therefore, Hedyotis diffusa extract-induced death of HL-60 cells is mediated by apoptotic signaling processes. The activity of Caspase 3-like proteases remained in a basal level in HL-60 cells treated with aqueous extract of Hedyotis diffusa. However, it was markedly increased in HL-60 cells treated with methanol extract of Hedyotis diffusa. In addition, the phosphotransferase activity of JNKl was increased in HL-60 cells treated with methanol extract of Hedyotis diffusa. Furthermore, the activation of transcriptional activator, $NF-{\kappa}B$ was markedly induced by methanol extract of Hedyotis diffusa. Anti-apoptotic Bc12 was cleaved into 23Kda fragment by treatment of methanol extract of Hedyotis diffusa. However, expression of proapoptotic Bax protein was increased by treatment of methanol extract of Hedyotis diffusa in a time-dependent manner. Furthermore, methanol extract markedly inhibited the colony forming efficiency of HL-60 cells in semisolid agar culture. Conclusions: Above results suggest that methanol extract of Hedyotis diffusa induces the apoptotic death of human leukemic HL-60 cells via activations of Caspase-3 proteases, JNKI, transcriptional activator $NF-{\kappa}B$, In addition, our results also suggest that methanol extract of Hedyotis diffusa reduces the malignant potential of HL-60 cells via down regulation of colony forming effciency through cleavage of Bc12 as well as induction of Bax.

• Journal of Life Science
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• v.21 no.6
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• pp.796-804
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• 2011

Microglia are central nervous system (CNS)-resident professional macrophages that function as the principal immune cells responding to pathological stimulations in the CNS. Activation of microglia, induced by various pathogens, protects neurons and maintains homeostasis in the CNS, but severe activation causes inflammatory responses secreting various neurotoxic molecules such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines. Allium fistulosum, a member of the onion family, is mainly cultivated for consumption, as well as medicinal use in Oriental medicine. It has been reported that A. fistulosum has various biological effects such as anti-oxidant, anti-platelet aggregation, anti-fungus and anti-cholesterol synthesis, however there has been no research about the anti-inflammatory effects of A. fistulosum extracts. In this study, it was undertaken to explore the functions of A. fistulosum as a suppressor of neuronal inflammation by using BV2 microglia cells. As a result, it was found that four kinds of extracts of A. fistulosum effectively reduced the expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at both mRNA and protein levels, and also attenuated pro-inflammatory cytokines such as tumor necrosis alpha (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6) at the mRNA level in BV2 stimulated by lipopolysaccharide (LPS). In addition, the extracts of A. fistulosum attenuated the release of NO markedly, as well as resulting in slight decreases of TNF-${\alpha}$ and IL-6 production, the effects of which were most significant when treated with ethyl alcohol extract from the whole A. fistulosum. In conclusion, the data indicated that the anti-inflammatory actions of A. fistulosum against BV2 microglia cells is through the down-regulation of iNOS, COX2 and pro-inflammatory cytokines such as TNF-${\alpha}$ and IL-6, and these effects are expected to help in the protection of nerve tissues by suppressions of neuronal inflammation in various neurodegenerative diseases.

• Journal of Life Science
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• v.24 no.12
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• pp.1339-1344
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• 2014

Inflammatory bowel disease is an immune disorder associated with chronic mucosal inflammation and severe ulceration in the gastrointestinal tract. Antibodies against proinflammatory cytokines, including TNF${\alpha}$, are currently used as promising therapeutic agents against the disease. Stabilization of the transcript is a crucial post-transcriptional process in the expression of proinflammatory cytokines. In the present study, we assessed the expression and histological distribution of the HuR protein, an important transcript stabilizer, in tissues from experimental animals and patients with Crohn's disease. The total and cytosolic levels of the HuR protein were enhanced in the intestinal epithelia from dextran sodium sulfate (DSS)-treated mice compared to those in control tissues from normal mice. Moreover, the expression of HuR was very high only in the mucosal and glandular epithelium, and the relative localization of the protein was sequestered in the lower parts of the villus during the DSS insult. The expression of HuR was significantly higher in mucosal lesions than in normal-looking areas. Consistent with the data from the animal model, the expression of HuR was confined to the mucosal and glandular epithelium. These results suggest that HuR may contribute to the post-transcriptional regulation of proinflammatory genes during early mucosal insults. More mechanistic investigations are warranted to determine the potential use of HuR as a predictive biomarker or a promising target against IBD.

• Journal of Ginseng Research
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• v.30 no.3
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• pp.117-127
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• 2006

Ginseng is a medicinal herb widely used in Asian countries. Dendritic cells(DCs) play a pivotal role in the initiation of T cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. In this study, we examined the effects of Red-ginseng(water extract, edible and fermented ethyl alcohol extract, crude saponin) on the DCs phenotypic and functional maturation. Immature DCs were cultured in the presence of GM-CSF and IL-4, and the generated immature DCs were stimulated by water extract, edible and fermented ethyl alcohol extract, crude saponin and LPS, respectively, for 24hours. The expression of surface co-stimulatory molecules, including MHC(major histocompatibility complex) class II, CD40, CD80 and CD86, was increased on DCs that were stimulated with crude saponin, but antigen-uptake capacity was decreased. The antigen-presenting capacity of Red-ginseng extracts-treated DCs as analyzed by allogeneic T cells proliferation and IL-2, $IFN-{\gamma}$ production was increased. Furthermore, $CD4^+$ and $CD8^+$ syngeneic T cell(OVA-specific) proliferation and $IFN-{\gamma}$ production was significantly increased. However, $CD4^+$ syngeneic T cell secreted higher levels of IL-2 in responding but not $CD8^+$ syngeneic T cell. These results indicate the immunomodulatory properties of Red-ginseng extracts, which might be therapeutically useful in the control of cancers and immunodeficient diseases through the up-regulation of DCs maturation.