• Journal of Korean Medicine Rehabilitation
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• v.24 no.3
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• pp.71-85
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• 2014

Objectives In this study, we investigated the inhibitory effects of Samhwangsasim-tang (S.H) on the allergic response caused by ovalbumin(OVA) sensitization and challenge in BALB/c mice. Methods The experimental animals were divided into five groups; 1) normal as negative control, 2) OVA-sensitized mice, 3) OVA-sensitized mice treated with 200 mg/kg of S.H 200, 4) OVA-sensitized mice treated with 400 mg/kg of S.H 400, and 5) OVA-sensitized mice treated with 5 mg/kg of Dexamethasone (Dex). Antigen sensitization for allergic mouse model was performed with twice injection of OVA for 2 weeks. After secondary injection, S.H was administrated orally into mice every day for 13 days and the inhibitory effect of S.H on allergic responses was evaluated. Results Treatment of S.H into allergic mice reduced significantly ear edema and infiltration of immune cells in ear tissues induced with OVA challenge in a dose-dependent manner. S.H reduced significantly the serum levels of Total Immunoglobulin(Ig)G and IgE, and particularly inhibited the production of OVA-specific IgE, but not OVA-specific IgG. The serum level of proinflammatory cytokine TNF-${\alpha}$ and Th2-associated cytokine IL-4 also were significantly decreased by S.H adminstration in a dose denpendent manner. S.H attenuated OVA-induced secretion of IFN-${\gamma}$, but not IL-12 which is a cytokine inducing the development of Th1 cells. It also reduced significantly the secretion of IL-4, which is a cytokine inducing the development of Th2 cells, after splenocytes were stimulated with OVA. However the secretion of IL-5 and IL-13 was influenced weakly or a little. Conclusions These results indicate that S.H could reduce the allergic response through inhibition of antigen-specific IgE and Th2-inducing cytokines. It suggest that S.H may be available clinically for the treatment of allergic patients.

• Journal of Periodontal and Implant Science
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• v.47 no.5
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• pp.292-311
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• 2017

Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal $CD4^+CD25^+CD127^{lo-}$ Tregs (127-Tregs) and $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an $NOD/scid/IL-2R{\gamma}^{-/-}$ mouse model of collagen-induced arthritis. Results: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of $CD4^+CD25^+$ Tregs at the articular joints in a mechanistic and orchestrated way. Conclusions: We propose human $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis.

• Journal of Life Science
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• v.24 no.10
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• pp.1118-1124
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• 2014

Porcine respiratory disease complex (PRDC) is a common respiratory disease in nursery and grow-finishing pigs. A complex of viral and bacterial agents is known to be involved in the etiology of PRDC. The purpose of this study was to investigate common etiologic agents associated with PRDC in the field and compare detection methods for identifying these agents. To understand the mechanism of polymicrobial infection in PRDC, changes in the expression of cytokines were investigated. In 461 pig samples examined, most of the affected pigs ranged from 3 to 10 weeks old (73.4%), and 348 (75.4%) samples were confirmed as polymicrobial infection. Of the polymicrobial-infected cases, two (50.3%), three (32.2%), four (13.8%), five (3.2%), and six (0.5%) agents were detected. Two- or three-agent infections were the most common, with PRRSV/PCV-2 (44.6%) the most common two-agent infection. PRRSV/PCV-2/H. parasuis (11.0%) was the most common three-agent infection. Comparison of two detection methods (PCR and IHC) in the polymicrobial cases showed that 78.4% were PCV-2 positive with the PCR method, and 26.2% were PCV-2 positive with IHC. SIV was 7.8% by the PCR method and 3.7% positive by the IHC. This result indicates that the PCR method is more useful than IHC for detecting causative agents in PRDC. In the analysis of cytokines in the two- and three-agent infected samples, interleukin (IL)-$1{\alpha}$, IL-2, IL-4, IL-6, IL-10, and INF-${\alpha}$ showed the same expression pattern. All cytokines were suppressed, except IL-6. These findings indicate that changes in cytokine expression could be used to understand the mechanism of polymicrobial infection in PRDC.

• Clinical and Experimental Pediatrics
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• v.48 no.8
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• pp.894-900
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• 2005

Purpose : Because of the unavailability of marrow transplantation, umbilical cord blood (CB) is increasingly being used. We evaluated the potential of ex vivo expansion and clonality in CD34+ cells separated from cord blood source and mobilized peripheral blood (PB) in a serum-free media. Methods : The CD34+ cells, selected from CB and mobilized PB, were expanded with hematopoietic growth factors. They were then cultured for burst-forming units of erythrocytes (BFU-E), colony-forming units of granulocytes and monocytes (CFU-GM) and colony-forming units of megakaryocytes (CFU-Mk) at culture days 0, day 4, day 7, and day 14 with various growth factors. Results : The CB-selected CD34+ cells showed significantly higher total cell expansion than those from the PB at day 7 (2 fold increase than PB). The CB-selected CD34+ cells produced more BFU-E colonies than did the PB on culture at days 7 and at day 14. Also, the CB-selected CD34+ cells produced more CFU-Mk colonies than did the PB on culture at day 4 and at day 7. Conclusion : The ex vivo expansion of the CB cells may be promising in producing total cellular expansion, CFU-Mk and BFU-E compared with PB for 7 to 14 days. The growth factors combination including megakaryocyte growth and development, flt3-ligand and interleukin-3 showed more expansion in the view of total cells and clonal maintenance compared with less combination.

• Journal of Nutrition and Health
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• v.51 no.3
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• pp.208-214
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• 2018

Purpose: Platycodon grandiflorum (a domestic diploid variety, DV-PG) has been used as a food and component of various traditional oriental medicines. Although DV-PG is known to have an anti-allergic effect, little is known about the beneficial health effects of the tetraploid 'Etteum' variety in the Platycodon grandiflorum (TV-PG), which is a recently developed variety. In this study, we investigated the effect of TV-PG on the rat basophilic leukemia mast cell (RBL-2H3)-mediated allergic response. Methods: To examine the effects of TV-PG on the allergic response, RBL-2H3 cells were sensitized with dinitropheny (DNP)-immunoglobin E, treated with various concentrations of TV-PG, and challenged with DNP-human serum albumin. We estimated cell granulation by measuring the release of ${\beta}$-hexosaminidase and production of inflammatory mediators by ELISA. Results: TV-PG had no effect on the proliferation or cytotoxicity of RBL-2H3 cells within the concentration range of 0 to $200{\mu}g/mL$. TV-PG inhibited degranulation of RBL-2H3 cells by antigen stimulation in a dose-dependent manner. TV-PG also suppressed the production of inflammatory cytokines and mediators such as interleukin-4, tumor necrosis $factor-{\alpha}$, prostagladin E2, and leukotriene B4 in RBL-2H3 cells by antigen stimulation. Conclusion: These results indicate that TV-PG exhibits anti-allergic activity via inhibition of degranulation as well as suppression of inflammatory mediators and cytokine release. These findings suggest that TV-PG may have potential as a preventive and therapeutic agent for the treatment of various allergic diseases.

• The Journal of Internal Korean Medicine
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• v.25 no.3
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• pp.427-439
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• 2004

It has been reported that Bopheyangyoungjeon(BYJ) has an effect on deficiency asthma(喘虛) clinically. The aim of this study was to determine an appropriate dosage of BYJ to treat asthma. In order to study the effects of orally administered BYJ on allergic asthma, mice were pretreated with three oral doses of the herbal solution of BYJ before antigen sensitization. 2 days later Mice were actively sensitized with a subcutaneous injection of ovalbumin and 13 day later ovalbumin aerosols were used to provoke asthmatic reaction. Serum level of IgE, IL-4, WBC, RBC, HGB, cell numbers in bronchoalveolar lavage fluid(BALF), and in vitro isometric contractile responses of the isolated tracheal smooth muscle(TSM) to acetylcholine(ACh, 0.1-1000uM), KCl were measured. The results were as follows ; 1. Contractile responses of TSM to ACh significantly increased in C group at Ach 0.3, 1, 3, 10, 30, 100, 300, 1000uM(P<0.05, P<0.01) and increased in D at 0.1, 0.3, 3, 30, 30, 100, 300, 1000uM. 2. The sensitivity of TSM to Ach increased more in A, B group, but it was not significant. 3. The maximal contractile response of TSM to ACh decreased more significantly in C group(P<0.01) and D group(P<0.05) the control group. 4. The maximal contractile response of TSM to KCI decreased more significantly in B group and C group(P<0.001) than in the control group. 5. The counts of lymphocytes in BALF decreased more significantly in B group and D group(P<0.05) than in the control group. 6. The counts of macrophages in BALF decreased more significantly in B group, C(P<0.05) than in the control group. 8. Serum IgE level increased more significantly in B group and C group(P<0.05) than the control group. 9. The counts of WBC, RBC, HGB in blood increased more significantly in A group than the control group. The above results support a role for BYJ orally administered in treatment of deficiency allergic Asthma.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.595-606
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• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

• The Journal of Internal Korean Medicine
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• v.31 no.2
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• pp.224-241
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• 2010

Objectives : The aim of the current study was to investigate the effects of Sargassum (Sargassum pallidum (TURN.) C. AG.; SP) on the experimental colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. Methods : ICR mice were divided into 7 groups (NOR, CON, $SS50\times5$, $SP20\times3$, $SP50\times3$, $SP20\times5$, $SP50\times5$). TNBS processing was intrarectally applied to all experimental groups on the 3rd experiment day, except the normal group (NOR). For investigating the prophylactic effect, SP at doses of 20 mg/kg ($SP20\times5$) and 50 mg/kg ($SP50\times5$) were orally administered for 5 days. The SP at doses of 20 mg/kg ($SP20\times3$) and 50 mg/kg ($SP50\times3$) were orally administered for 3 days after the colitis induction in order to check the effect of treatment. As a positive control group, sulfasalazine 50 mg/kg ($SS50\times5$) was administrated. Macroscopic findings of epithelial tissue on mice were measured by colon length and macroscopic score. Histologic findings were also checked by crypt cell, epithelial cell, inflammatory cell and edema of submucosa. We measured the ability of SP to inhibit lipid peroxidation and myeloperoxidase activity. We also measured levels of the inflammatory markers, interleukin (IL)-$1\beta$ and cyclooxygenase-2 (COX-2), its transcription factor activation, phospho-NF-${\kappa}B$ (pp65), in the colon by enzyme-linked immunosorbent assay and immunoblot analysis. We measured activation of fecal bacterial enzyme, $\beta$-glucuronidase and degradation activation of fecal glycosaminoglycan (GAG), and hyaluronic acid. Results : Oral administration of SP on mice inhibited TNBS-induced colon shortening and myeloperoxidase activity in the colon of mice as well as IL-$1\beta$ and COX-2 expression. SP also inhibited TNBS-induced lipid peroxidation and pp65 activation in the colon of mice. SP inhibited $\beta$-glucuronidase activation and fecal hyaluronic acid degradation activation as well. Conclusions : SP could be a possible herbal candidate and preventive prebiotic agent for treating inflammatory bowel disease (IBD). Further experiments to differentiate effects of SP on IBD, such as other solutions and extracting times, might be promising.

• Journal of Life Science
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• v.23 no.5
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• pp.682-688
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• 2013

We investigated a physiological function by fermenting a medicinal mushroom, (Cudrania tricuspidata fruit). A fermentation using lactic acid bacteria and the extracts isolated from 70% ethanol fractionation was included in cultured mouse spleen cells for cytokine secretion. As a result, total polyphenol content improved by 47% by organic acid fermentation. This was regarded as immune activity in fermented C. tricuspidata fruits, as the levels of interleukin (IL)-2 and IL-4 secretion increased. In addition, when the extracts were treated with a stimulant lipopolysaccharide, the secretion of helper T (Th) 1 cytokines IL-2, IL-12, and tumor necrosis factor-${\alpha}$ was suppressed, while the secretion of Th2 cytokines IL-4, IL-5, IL-6, and IL-10 significantly increased. Therefore, this study suggests that fermentative C. tricuspidata fruit extracts can contribute to the suppression of cellular immune reactions induced by the expression of Th1 cells and activation of the expression of Th2 cells inducing humoral immune reactions associated with the antibody generation by B lymphocytes.

• Journal of Ginseng Research
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• v.38 no.3
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• pp.167-172
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• 2014

Background: Roles of immune reaction and toll-like receptor-4 (TLR-4) have widely been established in the pathogenesis of alcoholic liver disease (ALD). Methods: We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol + urushiol, and alcohol + probiotics. Alcohol was administered via a LiebereDeCarli liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines, and histology, as well as the results of liver function tests were evaluated and compared. Results: No between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group ($0.37{\pm}0.06ng/mL$, $0.39{\pm}0.12ng/mL$, and $0.33{\pm}0.07ng/mL$, respectively, vs. $0.88{\pm}0.31ng/mL$; p < 0.05). Interleukin-$1{\beta}$ levels in liver tissues were decreased among the probiotics and KRG groups. The tumor necrosis factor-${\alpha}$ level of liver tissue was decreased in the KRG group. Conclusion: The pathological findings showed that alcohol-induced steatosis was significantly reduced by KRG and urushiol. As these agents improve immunologic capacity, they may be considered in potential anti-ALD treatments.