• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.385-392
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• 2011

Although monoculture methods have been remarkably useful due to their simplicity, they have serious limitation because of the different types of cells communication with each other in many physiological situations. We demonstrated levels of markers of endothelial dysfunction such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1$\beta$ (IL-1$\beta$) as well as stimulation of receptor of advanced glycation endproducts (AGEs) on monoand co-culture system such as only monocyte (THP-1) cultivation system, only endothelial cell (HUVEC) cultivation system, and co-cultivation system of THP-1 and HUVEC. The mRNA levels of TNF-$\alpha$ and IL-1$\beta$ on HUVEC increased by the co-culture with monocyte after 4 hr at 100 ${\mu}g/mL$ glyceraldehyde-AGE. The secreted protein contents into medium of TNF-$\alpha$ and IL-1$\beta$ increased after 8 hr approximately 2~2.5 times compared to mono-cultivation. In contrast, the mRNA level of receptor of AGE (RAGE) was relatively insensitive on the co-culture system. The mediators by which monocytes activate endothelial cell have not been fully elucidated. In this study we confirmed production of soluble cytokines such as TNF-$\alpha$ and IL-1$\beta$ by monocytes. Use of monocyte conditioned medium, which contains both cytokines, can activate endothelial cell.

• Microbiology and Biotechnology Letters
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• v.37 no.2
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• pp.160-169
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• 2009

Poly-$\gamma$-glutamic acid ($\gamma$-PGA) was mixed natural flora of Bacillus subtilis, contaminated from cooked soybeans. Also, it was performed to find out the antiallergic activity by using NC/Nga mice, in vitro. The $\gamma$-PGA (PGA-HM : PGA-high molecular weight), Molecular weight 300 kDa, was decomposed and made PGA-LM (PGA-low molecular weight) which has molecular weight below 30 kDa by sonication. Therefore, it was same result between PGA-HM and PGA-LM, and reported PGA-LM as basic result. We found that PGA-LM contains antiallergic efficacy that inhibit B cells and Th2 cells activation from isolated CD4+T cells in NC/Nga atopic dermatitis model mice, and not show a cytotoxicity in the hFCs. To investigate the effects of these PGA-LM in vitro, isolation of splenic B cell and CD4+ T cells in atopic dermatitis mice were used. To elucidate the role of PGA-LM in anti-CD40+ interleukin-4 (IL-4)-mediated B-cell activation, showed that the capacity of B cells to expression IL-$1\beta$, IL-6, and TNF-$\alpha$ mRNA down-regulated, and IL-10 mRNA up-regulation by PGA-LM treatment, but it had no effect on TGF-$\beta$ expression. In addition to CD4+IFN-$\gamma$+ and CD4+CD25+foxp3+, the functions of PGA-LM in the development of the CD4+CD25+foxp3+ and CD4+IFN-$\gamma$+cells, the phenotype and functions of PGA-LM induced CD4+CD25+foxp3+, and CD4+IFN-$\gamma$+cells in CD4+T cells. These results suggested that PGA-LM could change cytokine production and generate CD4+CD25+foxp3+ Tregs in NC/Nga mice, and may be effective for immunotherapy in patients with AD.

• Journal of Oriental Neuropsychiatry
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• v.23 no.1
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• pp.145-159
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• 2012

Objectives : This research investigates the effect of the JCT extract regarding Alzheimer's disease. Methods : The effects of the JCT extract on IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, NOS-II mRNA, APP mRNA, BACE mRNA, Nitric oxide(NO), and ${\beta}A$ protein production in the BV2 microglia cell lines treated with LPS and ${\beta}A$ were investigated. Results : 1. The JCT extract suppressed the expression of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, and NOS-II mRNA in BV2 microglial cell line treated with LPS and ${\beta}A$. 2. The JCT extract suppressed the expression of BACE and APP mRNA in BV2 microglial cell line treated with LPS and ${\beta}A$. 3. The JCT extract suppressed the expression of Nitric oxide(NO) in BV2 microglial cell line treated with LPS and ${\beta}A$. 4. The JCT extract suppressed the expression of ${\beta}A$ protein production in BV2 microglial cell line treated with LPS and ${\beta}A$. Conclusions : These results suggest that the JCT group may be effective for the treatment of Alzheimer's disease. Thus, JCT could be considered among the future therapeutic drugs indicated for the treatment of Alzheimer's disease.

• Journal of Oriental Neuropsychiatry
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• v.22 no.2
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• pp.107-128
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• 2011

Objectives : This experiment was designed to investigate the efficacy of DDTCMT hot water extract & ultra-fine powder on Alzheimer's Disease Model. Methods : The effects of the DDTCMT hot water extract on expression of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, NOS-II, IL-10, IL-1 receptor antagonist mRNA and production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in BV2 microglial cell line treated by lipopolysacchaide(LPS) were investigated. Expression of NO, ROS in BV2 microglial cell line treated by LPS and AChE activity in PC-12 cell treated by NGF were investigated. anti-AChE was observed through Western blot analysis. The effects of the DDTCMT hot water extract & ultra-fine powder on the behavior of the memory deficit mice induced by scopolamine were investigated. Results : 1. The DDTCMT hot water extract significantly decreased the production of mIL-6, mNOS-II, mTNF-${\alpha}$, and increased the production of mIL-10, mIL-1 receptor antagonist. 2. The DDTCMT hot water extract significantly suppressed the production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in BV2 microglial cell line treated by LPS. 3. The DDTCMT hot water extract significantly suppressed the NO and ROS production in BV2 microglial cell line treated by LPS. 4. The DDTCMT hot water extract groups showed inhibition of AChE activity in NGF treated PC-12 cell line. 5. The DDTCMT hot water extract suppressed anti-AChE expression in NGF treated PC-12 cell line was observed by Western blot analysis. 6. The DDTCMT hot water extract & ultra-fine powder groups showed significantly inhibitory effect on the scopolamine -induced impairment of memory in the experiment of Morris water maze. Conclusions : These results suggest that the DDTCMT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease.

• Journal of Korean Medical Science
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• v.33 no.52
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• pp.336.1-336.12
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• 2018

Background: We aimed to investigate mucosal immunity related to forkhead box P3 ($FOXP3^+$) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). Methods: Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-$ROR{\gamma}t$ antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin $(IL)-1{\beta}$, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon $(IFN)-{\gamma}$, soluble CD40L, and tumor necrosis factor-${\alpha}$. Results: $FOXP3^+$ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. $ROR{\gamma}t^+$ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 ($9.6{\pm}1.5$ vs. $12.7{\pm}3.0$), IL-21 ($14.9{\pm}1.5$ vs. $26.4{\pm}9.1$), IL-33 ($14.3{\pm}0.9$ vs. $19.1{\pm}5.3$), and $IFN-{\gamma}$ ($15.2{\pm}5.9$ vs. $50.2{\pm}42.4$) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 ($119.1{\pm}79.6$ vs. $52.9{\pm}39.1$) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A ($64.2{\pm}17.2$ vs. $28.3{\pm}10.0$) and IL-22 ($37.5{\pm}8.8$ vs. $27.2{\pm}3.7$) were significantly higher in ulcerative colitis than those in Crohn's disease. Conclusion: Mucosal immunity analysis showed increased $FOXP3^+$ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.

• Journal of Periodontal and Implant Science
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• v.31 no.4
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• pp.787-801
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• 2001

The molecular mechanisms control the function of PDL(periodonta1 ligament) cells and/or fibroblasts remain unclear. PDLsl7, PDL-specific gene, had previousely　identified the cDNA for a novel protein from cultured　PDL fibroblasts using subtraction hybridization between gingival fibroblasts and　PDL fibroblasts. The purpose　of this study was to determine the regulation by growth factors and cytokines on　PDLsl7 gene expression in　cultured human periodontal ligament cells and observe the immunohistochemical　localization of PDLsl7 protein in various tissues of mouse. Primary PDL fibroblasts isolated by scraping the root of the extracted human mandibular third molars. The cells were incubated with various concentration of human recombinant $IL-1{\beta}$, PDGF-BB and TGF\;${\beta}$ for 48h nd 2 weeks. At each time point total RNA was extracted and the levels of transcription ere assessed by reverse transcription-polymerase chain reaction (RT-PCR assay). polyclonal antiserum raised against PDLsl7 peptides, CLSVSYNRSYQINE and SEAVHETDLHDGC, were made, and stained the tooth, periodontium, developing bone, bone marrow and mid-palatal suture of the mouse. The results were as follows. 1. PDLsl7 mRNA levels were increased in response to PDGF (10ng/ml) and $TGF\;{\beta}$(20ng/ml) after treatment of the $IL-1{\beta}$, PDGF-BB and $TGF{\beta}$for 48 h. 2. PDLsl7 was up-regulated only by $TGF{\beta}$(20 ng/ml) after treatment of the $IL-1{\beta}$, PDGF-BB and $TGF\;{\beta}$ for 2 weeks and unchanged by the other stimulants. 3. PDLsl7 was a novel protein coding the 142 amino acid peptides in the ORF and the nucleotide sequences of the obtained cDNA from RT-PCR was exactly same as the nucleotides of the database. 4. Immunohistochemical analysis showed that PDLsl7 is preferentially expressed in the PDL, differentiating osteoblast-like cells and stromal cells of the bone marrow in the adult mouse. 5. The expression of PDLsl7 protein was barely detectable in gingival fibroblasts, hematopoetic cells of the bone marrow and mature osteocytes of the alveolar bone. These results suggest that PDLsl7 might upregulated by PDGF-BB or $TGF{\beta}$ and acts at the initial stage of differentiation when the undifferentiated mesenchymal cells in the bone marrow and PDL differentiate into multiple cell types. However, more research needs to be performed to gain a better understanding of the exact function of PDLsl7 during the differentiation of bone marrow mesenchymal and PDL cells.

• The Journal of Korean Medicine
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• v.30 no.4
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• pp.93-107
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• 2009

Objective: Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. However, there is not a satisfactory treatment for MN. This study aimed to evaluate the effect of Houttuyniae Herba Extract (HHE) on MN induced by cationic bovine serum albumin (cBSA). Methods: Mice were divided into 4 groups. The first group, Normal, was injected with saline. The second group, Control, was treated with cBSA (10mg/kg i.p) only. The third group, HHE-250, was treated with cBSA (10mg/kg i.p) and HHE (250mg/kg, p.o). The fourth group, HHE-500, was treated with cBSA (10mg/kg i.p) and HHE (500mg/kg, p.o). After treatment for 4 weeks, we measured change of body weight, 24 hrs proteinuria, serum albumin, total cholesterol, triglyceride, BUN, creatinine, IgA, IgM, IgG, TNF-${\alpha}$, IL-1${\beta}$ levels and the mRNA expression of IFN-${\gamma}$, IL-6, and IL-10. The morphologic changes of renal glomeruli were also observed with a light microscope and an electron microscope. Results: The levels of 24 hrs proteinuria and serum triglyceride, BUN, IgG, TNF-${\alpha}$, IL-1${\beta}$ significantly decreased in both HHE groups, while the level of serum albumin significantly increased in both HHE groups. The mRNA expression of IFN-${\gamma}$ and IL-6 in splenocytes considerably increased in both HHE groups. The mRNA expression of IL-10 in splenocytes considerably decreased in both HHE groups. In histological findings of kidney tissue, thickening of GBM decreased in both HHE groups. Conclusions: This study shows that HHE might be effective for treatment of acute stage MN. More clinical data and studies are to be done for efficient application.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.32 no.3
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• pp.58-76
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• 2019

Objectives : This study was designed to examine the effects of Daecheonglyong-tang(DCL) on atopic dermatitis induced by DNCB in mice Methods : The Nc/Nga mice were divided into 5 groups, and four groups excluding the normal group were applied by 2,4-dinitrochlorobenzene(DNCB), to cause AD and were orally administered with distilled water(negative control), dexamethasone(positive control), and DCL 200 or 400mg/kg once a day for 4 weeks respectively. The visual changes on skin, changes in skin tissue thickness and eosinophil infiltration were observed. IgE, Histamine, Cytokines, immune cells and the amount of gene expression of filaggrin, VEGF, $TGF-{\beta}1$, EGF were measured. Results : Dermatitis score showed a gross improvement on all DCL groups, similar to or better than positive control. All DCL groups showed no significant change in the basophils, while neutrophils and eosinophils decreased. In only DCL 400 mg/kg groups, white blood cells and mononuclear cells were decreased and lymphocytes were increased. In particular, neutrophils had similar or better effects than the positive control. In all DCL groups, IgE, Histamine, $IL-1{\beta}$, IL-4, IL-5, IL-6 and $TNF-{\alpha}$ were decreased and IL-2 was increased. In only DCL 400 mg/kg groups, IL-10 decreased and $IFN-{\gamma}$ increased. In particular, $IL-1{\beta}$ and $IFN-{\gamma}$ showed a similar rate of increase and decrease comparing positive control in DCL 400 mg/kg. $TGF-{\beta}$1 was increased in all DCL groups, filaggrin and VEGF were increased in only DCL 400 mg/kg groups. EGF did not make any changes. Epidermis, dermis thickness and eosinophil infiltration were also decreased in all DCL groups. Conclusions : By increasing Th1 cytokine and decreasing Th2 cytokine, DCL extracts appear to be effective in controlling immune response imbalances, anti-inflammatory and skin regeneration and are likely to be available as a treatment for AD.

• Korean Journal of Psychosomatic Medicine
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• v.28 no.2
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• pp.177-184
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• 2020

Objectives : Postpartum depression is known to occur in 10-15% of mothers. The concentration of cytokine varies depending on stress, depression, pregnancy and general medical conditions. We hypothesized that the concentration of cytokines may be related to reproduction and childbirth, and that women with postpartum depression would show alterations in cytokines levels. Methods : A total of 104 pregnant women were selected as subjects, and 60 non-pregnant women were selected as normal controls. Symptoms of depression were evaluated in the pregnant study subjects using the diagnostic criteria outlined in the Edinburgh Postnatal Depression Scale (EPDS). The pregnant subjects were divided into three groups perinatal non-depression controls (n=61), postpartum depression-recovery (n=18), and postpartum depression (n=25). Results : The plasma concentration of TGF-β1, IGF-1 was higher in the pregnant group than in non-pregnant controls (TGF-β1 ; p<0.01, IGF-1 ; p=0.026). At 24 weeks of pregnancy and 6 weeks of delivery, there were no significant differences in the plasma concentration of TGF-β1, IGF-1, β-NGF, IL-2, IL-4, IL-6, IFN-γ, TNF-α between the three groups. There was no statistically significant difference in all three groups during the course of depression in pregnant women. Conclusions : This study found significant difference in plasma cytokines concentrations between non-pregnant controls and perinatal non-depression controls.

• Korean Journal of Medicinal Crop Science
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• v.26 no.1
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• pp.8-18
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• 2018

Background: This present study was conducted to evaluate the anti-inflammatory and immune regulatory effects of Aucklandia lappa Decne (AL). Methods and Results: We measured cytotoxicity, nitric oxide (NO) content, mRNA expression (iNOS, IL-1${\alpha}$, IL-$1{\beta}$, and TNF-${\alpha}$), protein expression (iNOS, COX-2, and $I{\kappa}B$) and phagocytic activity in RAW264.7 cells. Male BALB/c mice were fed 100 mg/kg AL (Aucklandia lappa Decneon 70% ethanol extract) and 250 mg/kg AL for 4 weeks; thereafter, we observed B/T or $CD4^+/CD8^+$ lymphocyte subpopulation change, and expression patterns of $CD4^+$ and $CD8^+$ lymphocytes by immunohistochemical staining in mouse splenocytes and/or thymocytes. To determine the experimental concentration of AL, cell viability was measured by MTT assay and tested at $12.5{\mu}g/m{\ell}$ or less. AL inhibited the levels of NO, lymphokine production (IL-$1{\beta}$, and TNF-${\alpha}$), and mRNA (iNOS, IL-1${\alpha}$, IL-$1{\beta}$, and TNF-${\alpha}$) and protein (iNOS, and COX-2) expression. Additionally, the levels of $I{\kappa}B$, phagocytic activity, and splenic and thymic T lymphocytes, especially $T_H$ and $T_C$ cells were significantly increased in AL administered mice. The immuno-reactive density of $CD4^+$ and $CD8^+$ lymphocytes was stronger in AL groups than in the normal group. AL stimulated NO, iNOS, and COX-2, and regulated IL-1${\alpha}$, IL-$1{\beta}$, TNF-${\alpha}$, and $I{\kappa}B$ in macrophages treated with LPS (lipopolysaccharide). In addition, AL increased the phagocytic activity of macrophages and the immunity of mouse T ($T_H$, and $T_C$) cells. Conclusions: These results suggested that AL might show anti-inflammatory activity via the suppression of various inflammatory markers and immuno-regulatory activity.