• Parasites, Hosts and Diseases
• /
• v.50 no.4
• /
• pp.385-390
• /
• 2012

In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of $CD4^+CD25^+Foxp3^+$ T (regulatory T; $T_{reg}$) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-${\gamma}$, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-${\beta}$, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of $T_{reg}$ cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and $T_{reg}$ cells recruitment.

• The Journal of Korean Medicine
• /
• v.26 no.1 s.61
• /
• pp.59-70
• /
• 2005

Objective: Tumor necrosis factor-a $(TNF-{\alpha})$, a potent immuno-modulator and pro-inflammatory cytokine, has been implicated in many pathological processes. In this study, the author examined whether promoter region polymorphism in the $TNF-{\alpha}$a gene at position-308 affect the odds of cerebral infarction (CI) and whether genetic risk is enhanced by sasang constitutional classification. Methods: 212 CI patients and 610 healthy controls were genotyped and determined according to sasang constitutional classification. The amplified genotypes were analyzed on $8\%$ polyacrylamide gel. The alleles were visualized by ethidium bromide staining. Primers for $TNF-{\alpha}$ were designed to incorporate a polymorphic site at a position -308 bp of the $TNF-{\alpha}$ gene into an NcoI restriction site. Restriction digests generated products of 87 and 20 bp for G allele and 107 bp for A allele. Results : A significant decrease was found for the $TNF-{\alpha}$ A allele in CI patients compared with controls (P=0.033, odds ratio, O.R.: 0.622). However, there was no significant association between $TNF-{\alpha}$ polymorphism and sasang constitution in CI patients. Conclusion: My finding suggests that $TNF-{\alpha}$promoter region polymorphism is responsible for susceptibility to CI in Koreans.

• IMMUNE NETWORK
• /
• v.11 no.6
• /
• pp.358-363
• /
• 2011

Background: Traditionally, interferon-${\gamma}$ (IFN-${\gamma}$) was regarded as a pro-inflammatory cytokine, however, recent reports suggested role of IFN-${\gamma}$ in immune tolerance. In our previous report, we could induce tolerance to male antigen (HY) just by male islet transplantation in wild type C57BL/6 mice without any immunological intervention. We tried to investigate the influence of IFN-${\gamma}$ deficiency on tolerance induction by male islet transplantation. Methods: To examine the immunogenicity of male tissue in the absence of IFN-${\gamma}$, we transplanted male IFN-${\gamma}$ knock-out (KO) skin to female IFN-${\gamma}$ KO mice. Next, we analyzed male IFN-${\gamma}$ KO islet to streptozotocin-induced diabetic female IFN-${\gamma}$ KO mice. And, we checked the functionality of grafted islet by graft removal and insulin staining. Results: As our previous results in wild type C57BL/6 mice, female IFN-${\gamma}$ KO mice rejected male IFN-${\gamma}$ KO skin within 29 days, and did not reject male IFN-${\gamma}$ KO islet. The maintenance of normal blood glucose level was dependent on the presence of grafted male islet. And the male islet recipient did not reject 2nd challenge of male islet graft also. Conclusion: Deficiency of IFN-${\gamma}$ does not have influence on the result of male skin graft and male islet transplantation. Conclusively, male islet transplantation induced T cell tolerance is not dependent on the presence of IFN-${\gamma}$.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.33 no.1
• /
• pp.48-55
• /
• 2019

Current studies have been reported that fruits such as berries may contain both antioxidant and antitumor polyphenols that may be important in this regard. We investigated the immunostimulatory effect of fermented blueberry (Vaccinium corymbosum L.) on cyclophosphamide-induced immunosuppression in animal model. Rats were administered blueberry yeast fermented powder (BYFP) at doses 30, 100, and 300 mg/kg for 4 weeks after cyclophosphamide (Cy) treatment, respectively. The immunomodulatory effect of BYFP were measured both in vitro and in vivo, and the changes of blood components were also analyzed. We found that BYFP recovered immunosuppression-mediated decreased liver, spleen, and thymus weights as well as up regulation of white blood cell, lymphocyte, and neutrophil in blood. Moreover, BYFP up-regulated IL-2, TNF-${\alpha}$, and IFN-${\gamma}$ pro-inflammatory cytokine production compared to immune suppressed control group, respectively. According to histological studies, BYFP regenerated significantly on Cy-mediated injured spleen at the high doses (BYFP 300) comparison with Cy-treated groups (immunosuppression). Collectively, these findings suggest that BYFP may have the potential as a dietary immunostimulatory agent.

• Journal of fish pathology
• /
• v.34 no.1
• /
• pp.23-29
• /
• 2021

Interferon regulatory factors (IRFs) are a family of transcription factors essential to the control of antiviral immune response, cell growth, differentiation and apoptosis. IRF10 of zebrafish (Danio rerio) was negative regulation of the interferonΦ1 and 3 response in vitro. In this study, we analyze the induction of in vivo immune response activation from the IRF10 gene of zebrafish and the protective effect against VHSV. As the results, the group inoculated with IRF10 expression vectors, there was no expression of IFNΦ1, suggestion that IRF10 may function as a negative regulator of IRF3, which binds to the IFNΦ1 promoter. And other types of interferon genes (IFNΦ2-4) are thought to have been activated, inducing to the expression of pro-inflammatory cytokine and Mx genes. As the results of challenge test performed at 14 days after inoculation of the expression vectors, the maximum survival rate [50% (1㎍ DNA) and 42.5% (10㎍ DNA)] for IRF10 group were recorded. Meanwhile, the survival rates of pcDNA3.1 and PBS as the control groups were 10% and 15%, respectively. This study suggests that the possibility that activation of IRF10 molecule could be exploited as a VHS control method.

• Journal of Korean Medicine Rehabilitation
• /
• v.31 no.1
• /
• pp.1-16
• /
• 2021

Objectives This study was designed to evaluate the effects of Danggwisu-san (Dangguixu-san, DG) on bone repair from femur fracture in mice. Methods Mice were randomly divided into 4 groups (normal, control, positive control and DG 300 mg/kg-treated group). In order to investigate the effects of DG on gene expressions in experimental animals with fracture, we measured the levels of bone morphogenetic protein-2 (BMP2), cyclooxygenase-2 (COX2), Sox9, collagen type II alpha 1 chain (Col2a1), runt-related transcription factor 2 (Runx2), osterix genes. After the cytotoxicity test, we analyzed the levels of expression of osteocalcin and Runx2, and tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine. The process of fusion in the fracture was also investigated by gross examination. Results Through in vivo BMP2, COX2 gene expression significantly decreased. Sox9 significantly increased. Col2a1, Runx2, osterix gene expression also increased as well, but there was no statistical significance. The degree of unilateral fracture fusion investigated by gross examination was significantly faster than those of the other groups. Through in vitro the level of TNF-α in macrophages was increased by DG in a dose-dependent mannerand and 250 and 500 ㎍/mL showed statistical significance. Osteocalcin and Runx2 genes expressions increased when DG was treated in osteoblasts. Conclusions DG promotes the healing of the fracture through the expression of bone repair-related genes and TNF-α production. This study may set the foundation for the clinical application of DG to the patients with bone fractures.

• Biomolecules & Therapeutics
• /
• v.29 no.5
• /
• pp.492-497
• /
• 2021

Levels of sphingosine 1-phosphate (S1P), an intercellular signaling molecule, reportedly increase in the bronchoalveolar lavage fluids of patients with asthma. Although the type 4 S1P receptor, S1P₄ has been detected in mast cells, its functions have been poorly investigated in an allergic asthma model in vivo. S1P₄ functions were evaluated following treatment of CYM50358, a selective antagonist of S1P₄, in an ovalbumin-induced allergic asthma model, and antigen-induced degranulation of mast cells. CYM50358 inhibited antigen-induced degranulation in RBL-2H3 mast cells. Eosinophil accumulation and an increase of Th2 cytokine levels were measured in the bronchoalveolar lavage fluid and via the inflammation of the lungs in ovalbumin-induced allergic asthma mice. CYM50358 administration before ovalbumin sensitization and before the antigen challenge strongly inhibited the increase of eosinophils and lymphocytes in the bronchoalveolar lavage fluid. CYM50358 administration inhibited the increase of IL-4 cytokines and serum IgE levels. Histological studies revealed that CYM50358 reduced inflammatory scores and PAS (periodic acid-Schiff)-stained cells in the lungs. The pro-allergic functions of S1P₄ were elucidated using in vitro mast cells and in vivo ovalbumin-induced allergic asthma model experiments. These results suggest that S1P₄ antagonist CYM50358 may have therapeutic potential in the treatment of allergic asthma.

• Tuberculosis and Respiratory Diseases
• /
• v.85 no.1
• /
• pp.18-24
• /
• 2022

Background: Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is a bronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthma treatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect of TIO on NeuA compared to that of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilic inflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and 23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL) and lung homogenates, and lung tissue histopathology were compared between the two groups. Results: Neutrophil counts, T helper 2 cells (T_H2)/T_H17 cytokines, and pro-inflammatory cytokine in BAL fluids were elevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluids than the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group but elevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in the TIO group than in the NeuA group (all p<0.05). Conclusion: TIO showed more potent effects than DEX in improving airway inflammation and attenuating airway resistance in NeuA.

• Journal of Animal Science and Technology
• /
• v.64 no.6
• /
• pp.1092-1104
• /
• 2022

Using antibiotics as growth promoter has been banned in poultry feed industry, thus various researchers try to seek an alternative to replace the growth-promoting antibiotics. In this study, we aimed to evaluate the growth performance via intestinal nutrient utilization and cecal microbial composition of broiler after dietary supplementation with most commonly using antibiotics, zinc bacitracin, and sophorolipid. A total of 180 1-day-old chicks were randomly assigned, and dietary treatment was as follow: CON, basal diet; ZB, 100 ppm of zinc bacitracin supplemented diet; and SPL, 250 ppm of sophorolipid supplemented diet. Their growth performance was evaluated and the samples of blood, small intestine, and ileal and cecal digesta were collected for biochemical, histological, and genomic analyses. The body weight and average daily gain of 7-day-old chicks were higher in ZB and those in overall experimental period were improved by ZB and SPL supplementation (p < 0.05). Their intestinal characteristics were not affected by dietary treatments in duodenum and ileum. Nonetheless, villus height was increased by SPL supplementation in jejunum (p < 0.05). Moreover, dietary SPL supplementation could down-regulate the expression level of pro-inflammatory cytokine, IL-1β (p < 0.05). mRNA levels of lipid and protein transporters did not differ among the treatments, however, relative expression levels of carbohydrate transporters, GLUT2 and SGLT1 were increased in broiler chicken's jejumum fed zinc bacitracin and sophorolipid supplemented diets (p < 0.05). Dietary zinc bacitracin supplementation could increase the population of Firmicutes in phylum level, and the portion of Turiciacter in genus level. On the other hands, the portion of Faecalibacterium was increased by dietary SPL supplementation compared to the other treatments. Our findings suggest that SPL supplementation improves growth performance through enhanced carbohydrate utilization capacity via improvement of gut morphological status and modulation of the cecal microbial population of broilers.

• Journal of Microbiology and Biotechnology
• /
• v.33 no.4
• /
• pp.441-448
• /
• 2023

Brucellosis is a contagious zoonotic disease that infects millions of people annually with hundreds of millions more being exposed. It is caused by Brucella, a highly infectious bacterial species capable of infecting humans with an estimated dose of 10-100 organisms. Sirtuin 1 (SIRT1) has been reported to contribute to prevention of viral diseases as well as a chronic infection caused by Mycobacterium bovis. Here, we investigated the role of SIRT1 in the establishment of Brucella abortus infection in both in vitro and in vivo systems using the reported SIRT1 activators resveratrol (RES), piceatannol (PIC), and ginsenoside Rg3 (Rg3). In RAW264.7 cells, SIRT1 activators did not alter the adherence of Brucella or Salmonella Typhimurium. However, reduced uptake of Brucella was observed in cells treated with PIC and Rg3, and survival of Brucella within the cells was only observed to decrease in cells that were treated with Rg3, while PIC treatment reduced the intracellular survival of Salmonella. SIRT1 treatment in mice via oral route resulted in augmented Brucella resistance for PIC and Rg3, but not RES. PIC treatment favors Th2 immune response despite reduced serum pro-inflammatory cytokine production, while Rg3-treated mice displayed high IL-12 and IFN-γ serum production. Overall, our findings encourage further investigation into the complete mechanisms of action of the different SIRT1 activators used as well as their potential benefit as an effective alternative approach against intracellular and extracellular pathogens.