• 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.

• Journal of Periodontal and Implant Science
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• v.34 no.3
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• pp.607-622
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• 2004

Recently epidemiologic studies have indicated that the patients with periodontitis may have increased risk of ischemic cardiovascular events, and have suggested the important roles of blood cytokines and acute reactant proteins in the systemic infection and inflammatory response. Periodontitis and coronary heart disease (CHD) may share the common risk factors and the genetic mechanism associated with interleukin(IL)-1A, B and RA genotype may be involved in the production of IL-1. This study was aimed to investigate the relationship between angiographically defined CHD and periodontitis as chronic Gram-negative bacterial infection and to determine whether the IL-1 gene polymorphism is associated in both diseases. Patients under the age of 60 who had undergone diagnostic coronary angiography were enrolled in this study. Subjects were classified as positive CHD (+CHD, n=37) with coronary artery stenosis more than 50% in at least one of major epicardial arteries, and negative CHD (-CHD, n=30) without significant stenosis. After recording the number of missing teeth, periodontal disease severity was measured by means of plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and radiographic bone loss around all remaining teeth. Gingival crevicular fluid (GCF) was collected from the 4 deepest periodontal pockets and assessed for cytokine ($IL-1{\beta}$, IL-6, IL-1ra, tumor necrosis $factor-{\alpha}$, and prostaglandin $E_2$). Additionally, blood CHD markers, lipid profile, and blood cytokines were analyzed. IL-1 gene cluster genotyping was performed by polymerase chain reaction and enzyme restriction using genomic DNA from buccal swab, and allele 2 frequencies of IL-1A(+4845), IL-1B(+3954), IL-B(-511), and IL-1RA(intron 2) were compared between groups. Even though there was no significant difference in the periodontal parameters between 2 groups, GCF level of $PGE_2$ was significantly higher in the +CHD group(p<0.05). Correlation analysis showed the positive relationship among PD, CAL and coronary artery stenosis(%) and blood $PGE_2$. There was also significant positive relationship between the periodontal parameters (PI, PD, CAL) and the blood CHD markers (leukocyte count, C-reactive protein, and lactic dehyrogenase). IL-1 gene genotyping showed that IL-1A(+3954) allele 2 frequency was significantly higher in the +CHD group compared with the -CHD group (15% vs. 3.3%, OR 5.118,p=0.043). These results suggested that periodontal inflammation is related to systemic blood cytokine and CHD markers, and contributes to cardiovascular disease via systemic inflammatory reaction. IL-1 gene polymorphism might have an influence on periodontal and coronary heart diseases in Korean patients.

• Tuberculosis and Respiratory Diseases
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• v.81 no.1
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• pp.80-87
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• 2018

Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of $T_H2$ process and increased $T_H1$ and/or $T_H17$ process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon ${\gamma}$, and tumor necrosis factor ${\alpha}$ in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

• Journal of Life Science
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• v.22 no.10
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• pp.1307-1315
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• 2012

We evaluated the effect of dietary supplements with benzoic acid on intestinal beneficial bacteria concentration and immune response of weaning pigs. Supplementation with benzoic acid at 0.5% or control diet for 35 days resulted in a higher Lactobacillus casei concentration in the cecum. Supplementation with benzoic acid at 0.5% increased concentration of L. plantarum in the cecum. Pigs with the control diet and 0.5% benzoic acid had significantly increased concentration of B. subtillis in the cecum compared to the antibiotic group, while the concentration of B. subtillis in the rectum increased in pigs given 0.3 and 0.5% benzoic acid (p<0.05). Compared with the control group, the level of interleukin-$1{\beta}$ mRNA showed a significant decrease in the proximal small intestine in pigs fed diets supplemented with benzoic acid at 0.5% or antibiotic. Feeding 0.5% benzoic acid resulted in a marked reduction in the expression of IL-6 mRNA in the middle small intestine (p<0.05). Supplementation with benzoic acid at 0.5% or antibiotic resulted in a lower level of tumor necrosis factor-mRNA in the middle intestine. Up to 0.5% benzoic acid may be included in weaning diets for improvement of intestinal beneficial bacteria, thus modulating genes of pro-inflammatory cytokines in the gastrointestinal tract.

• Journal of Society of Preventive Korean Medicine
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• v.18 no.1
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• pp.125-138
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• 2014

Objective : Polycan, exopolymers purified from Aureobasidium pullulans SM-2001 and calcium gluconate have been showed favorable inhibitory effects on the periodontitis and related alveolar bone losses through antioxidant and anti-inflammatory activities, respectively. In the present study, we intended to observe the possible synergic effects of mixed formula consisted of Polycan and calcium gluconate on ligation-induced experimental periodontitis and related alveolar bone losses in rats, and to select the fittest compositions for further developing as effective agents to ameliorate periodontal diseases. Method : Experiments were conducted as two separated two tests - first is synergic effects of Polycan and calcium gluconate 1:1, 1:9 and 9:1 mixtures, and second is 1:99, 2:98, 4:96, 8:92 and 1:9 mixtures. Experimental periodontal diseases were induced by ligature placed around the cervix of upper left incisior teeth of rats. One day after ligation placements, 200mg/kg of each single or mixed formulas of Polycan or/and calcium gluconate were orally administered for 10 days. The changes on the alveolar bone loss index and maxillary bone mineral density (BMD) were observed for detecting alveolar bone losses, and for anti-inflammatory effects, myeloperoxidase (MPO) activities and proinflammatory cytokine (tumor necrosis factor; TNF-${\alpha}$) contents were also evaluated in gingival tissues around ligature placed incisior teeth. The results of mixtures were compared with those of singe Polycan and calcium gluconate treated rat. Results : Each single or mixed formulas of Polycan or/and calcium gluconate favorably and significantly inhibited the inflammatory changes. The inhibitory effects of mixed formula consisted of Polycan and calcium gluconate 1:9 showed against periodontitis and related alveolar bone losses as compared with those of each Polycan and calcium gluconate single formula (p<0.05). In second experiment, Polycan and calcium gluconate 2:98, 4:96, 8:92 and 1:9 mixed formulas also showed significant increased anti-inflammatory and inhibitory effects against alveolar bone losses as compared with those of each single formula. Among them, Polycan and calcium gluconate 2:98 showed the highest efficacy against to ligation-induced experimental periodontitis and related alveolar bone losses. Conclusion : The results obtained in this study suggest that appropriated mixtures of Polycan and calcium gluconate showed synergic inhibitory effects against ligation-induced experimental periodontitis and related alveolar bone losses in rats. Moreover, Polycan and calcium gluconate 2:98 showed the highest efficacies in this experiment, suggesting the fittest composition for further developing as effective agents to ameliorate periodontal diseases.

• Mycobiology
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• v.45 no.4
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• pp.297-311
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• 2017

Saprolegniasis is one of the most devastating oomycete diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated oomycete belongs to the member of S. parasitica, supported by its typical features including cotton-like mycelium, zoospores and phylogenetic analysis with internal transcribed spacer region. Pathogenicity of isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as a disease model. Host-pathogen interaction in adult zebrafish was investigated at transcriptional level. Upon infection with S. parasitica, pathogen/antigen recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility complex class I), pro/anti-inflammatory cytokines (interleukin $[IL]-1{\beta}$, tumor necrosis factor ${\alpha}$, IL-6, IL-8, interferon ${\gamma}$, IL-12, and IL-10), matrix metalloproteinase (MMP9 and MMP13), cell surface molecules ($CD8^+$ and $CD4^+$) and antioxidant enzymes (superoxide dismutase, catalase) related genes were differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia agent, plant based lawsone was applied to investigate on the susceptibility of S. parasitica showing the minimum inhibitory concentration and percentage inhibition of radial growth as $200{\mu}g/mL$ and 31.8%, respectively. Moreover, natural lawsone changed the membrane permeability of S. parasitica mycelium and caused irreversible damage and disintegration to the cellular membranes of S. parasitica. Transcriptional responses of the genes of S. parasitica mycelium exposed to lawsone were altered, indicating that lawsone could be a potential anti-S. parasitica agent for controlling S. parasitica infection.

• Journal of Oriental Neuropsychiatry
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• v.30 no.4
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• pp.357-369
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• 2019

Objectives: This study was designed to examine the effect of Hominis Placenta Pharmacopuncture on the change in behavior, sleep-related hormones, inflammatory cytokines, anti-oxidants, weight, blood, and serum on rats given chronic physical stress. Methods: Wistar rats older than age 10 weeks were used in this experiment. They were divided into six groups. The normal group was not given stress. The control group was given only chronic physical stress and no treatment. The positive control group was given chronic physical stress and treated with zolpidem. Three Hominis Placenta Pharmacopuncture (HPP) groups were given chronic physical stress, then treated with different concentrations of HPP; HPP-0.5× (0.5 times diluted), HPP-1× (undiluted) and HPP-2× (2 times condensed). The changes of values of Nestlet Shredding results, weight, Melatonin, Gamma-aminobutylic Acid (GABA), Tumor Necrosis Factor Alpha (TNF-α), Interleukin-6 (IL-6), Superoxide dismutase (SOD), glutathione peroxidase (GPx), AST, ALT, BUN, Creatinine, and leukocytes were observed during the experiment. Results: The changes in chronic physical stress of the rat model were as follow. The Nestlet Shredding result increased in the control group compared to the normal group (p<0.05), and decreased in the HPP-1× and HPP-2× compared to the control group (p<0.05). The amount of weight gain showed increasing tendency in the HPP-2× compared to the control group since the second week. The GABA increased (p<0.05) and Melatonin also showed certain increasing tendency in the HPP-1× and HPP-2× compared to the control group. The TNF-α and IL-6 increased in the control group compared to the normal group (p<0.01), and decreased in all the HPPs compared to the control group (p<0.05). The SOD level decreased in the control group compared to the normal group (p<0.01), and increased in all the HPPs compared to the control group (p<0.05). GPx, AST, ALT, Bun, Creatinine and leukocytes showed no noticeable difference among all groups. Conclusions: Hominis Placenta Pharmacopuncture was effective in increasing weight, GABA, Melatonin, SOD, and decreasing Nestlet Shredding and inflammatory cytokines, suggesting that it consequently facilitates in relieving physical stress.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.3
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• pp.445-451
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• 2016

This study demonstrated the immunological effects of methanol extracts from Doenjang added with wild plants (Pteridium aquilinum and Aster scaber) on bone-marrow derived macrophages and mouse splenocytes. Doenjang (DJ) and wild plant added Doenjang (WPDJ) extracts were treated to bone-marrow derived macrophages (BMDM) and splenocytes, and cell proliferation and cytokine production were measured. Cell proliferation of BMDM and splenocytes was more highly elevated in the WPDJ-treated group compared to the DJ-treated group. Cytokine [tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, IL-10, and IL-12] production in BMDM also significantly increased in the WPDJ-treated group. Similarly, in the case of cytokine production in splenocytes, WPDJ treatment highly increased production of Th 1 type cytokines [interferon (IFN)-${\gamma}$ and IL-2] but did not affect production of Th 2 type cytokines (IL-4). These results suggest that wild plants could improve the immunomodulatory activity of Doenjang and may be effective for the development Doenjang.

• Allergy, Asthma & Immunology Research
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• v.10 no.6
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• pp.628-647
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• 2018

Purpose: Obesity is associated with metabolic dysregulation, but the underlying metabolic signatures involving clinical and inflammatory profiles of obese asthma are largely unexplored. We aimed at identifying the metabolic signatures of obese asthma. Methods: Eligible subjects with obese (n = 11) and lean (n = 22) asthma underwent body composition and clinical assessment, sputum induction, and blood sampling. Sputum supernatant was assessed for interleukin $(IL)-1{\beta}$, -4, -5, -6, -13, and tumor necrosis factor $(TNF)-{\alpha}$, and serum was detected for leptin, adiponectin and C-reactive protein. Untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolic profiles in sputum, serum and peripheral blood monocular cells (PBMCs) were analyzed by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and pathway topology enrichment analysis. The differential metabolites were further validated by correlation analysis with body composition, and clinical and inflammatory profiles. Results: Body composition, asthma control, and the levels of $IL-1{\beta}$, -4, -13, leptin and adiponectin in obese asthmatics were significantly different from those in lean asthmatics. OPLS-DA analysis revealed 28 differential metabolites that distinguished obese from lean asthmatic subjects. The validation analysis identified 18 potential metabolic signatures (11 in sputum, 4 in serum and 2 in PBMCs) of obese asthmatics. Pathway topology enrichment analysis revealed that cyanoamino acid metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, pentose phosphate pathway in sputum, and glyoxylate and dicarboxylate metabolism, glycerolipid metabolism and pentose phosphate pathway in serum are suggested to be significant pathways related to obese asthma. Conclusions: GC-TOF-MS-based metabolomics indicates obese asthma is characterized by a metabolic profile different from lean asthma. The potential metabolic signatures indicated novel immune-metabolic mechanisms in obese asthma with providing more phenotypic and therapeutic implications, which needs further replication and validation.

• 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.