• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.408-412
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• 2004

For the evaluation of immunomodulatory effect of Korean Oldenlandiae Herb (OH) and Radix (OR), our experiment was performed with methanol extracts of Korean Oldenlandiae Herba and Radix. After administration of methanol extracts of Korean OH and OR for 7 days, Balb/C mice were immunized with sheep red blood cells. Four days later, splenic leukocytes were isolated and immunological experiments were performed. Rosette forming cells and plaque forming cells were significantly increased in Korean OH and OR treated mice compared with PBS treated control. Korean OH and OR also enhanced T and B lymphocytes, macrophage and natural killer cells by flowcytometric analysis. LPS-induced TNF-α and IL-6 levels were increased by OH and OR compared with untreated control. These results suggest that Korean OH and OR have immunomodulatory activity through regulation of cell-mediated immune and humoral immune response.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.4
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• pp.524-531
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• 2005

Two experiments were conducted to standardize in ovo injection of amino acids (AA) and to evaluate the effect of in ovo injection of limiting AA(s) on pre and post hatch growth performance, immune response and development of digestive organs. Combinations of essential and non-essential amino acids (Lys+Arg, Lys+Met+Cys, Thr+Gly+Ser, Ile+Leu+Val and Gly+Pro) were injected into 50 eggs in each treatment group at 14 d of embryonic age. Standardization of injection site, needle length and embryonic age revealed that when AA were injected in to the broad end of the egg with a 11 mm needle and at the narrow end with a 24 mm needle both at the 7$^{th}$ and 14$^{th}$ d of incubation there was poor hatchability. However, better hatchability was recorded when the AA were injected in the narrow end of the egg with a 11 mm needle and in the broad end with a 24 mm needle on the 14$^{th}$ d of incubation. The chick to egg weight ratio was higher (p<0.018) when AA were injected on the 14$^{th}$ d of incubation. When a combination of amino acids were injected a 63.6 or 63.2 g difference in body weight of bird at 21 d was recorded between uninjected control and Ile+Leu+Val or Gly+Pro group, respectively. Higher feed intake (p<0.047) was recorded in the AA injected groups and feed conversion ratio (FCR) was numerically better in Gly+Pro, Lys+Met+Cys AA injected groups than in the uninjected control. Significantly higher immune response to cell mediated (p<0.033) and humoral (p<0.002) immunity was observed in in ovo amino acid injected birds, especially in Lys+Met+Cys, Thr+Gly+Ser or Ile+leu+Val groups. The digestive organ weights at 21 d did not differ between specific AA injected groups and the uninjected control. In ovo injected amino acids may act as immunomodulators and their role in gastrointestinal development needs further research.

• Journal of Microbiology and Biotechnology
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• v.22 no.6
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• pp.856-865
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• 2012

We describe the construction and immunobiological properties of a novel whooping cough vaccine candidate, in which the aroQ gene, encoding 3-dehydroquinase, was deleted by insertional inactivation using the kanamycin resistance gene cassette and allelic exchange using a Bordetella suicide vector. The aroQ B. pertussis mutant required supplementation of media to grow but failed to grow on an unsupplemented medium. The aroQ B. pertussis mutant was undetectable in the trachea and lungs of mice at days 6 and 12 post-infection, respectively. Antigen-specific antibody isotypes IgG1 and IgG2a, were produced, and cell-mediated immunity [CMI], using interleukin-2 and interferon-gamma as indirect indicators, was induced in mice vaccinated with the aroQ B. pertussis vaccine candidate, which were substantially enhanced upon second exposure to virulent B. pertussis. Interleukin-12 was also produced in the aroQ B. pertussis-vaccinated mice. On the other hand, neither IgG2a nor CMI-indicator cytokines were produced in DTaP-vaccinated mice, although the CMI-indicator cytokines became detectable post-challenge with virulent B. pertussis. Intranasal immunization with one dose of the aroQ B. pertussis mutant protected vaccinated mice against an intranasal challenge infection, with no pathogen being detected in the lungs of immunized mice by day 7 post-challenge. B. pertussis aroQ thus constitutes a safe, non-reverting, metabolite-deficient vaccine candidate that induces both humoral and cell-mediated immune responses with potential for use as a single-dose vaccine in adolescents and adults, in the first instance, with a view to disrupting the transmission cycle of whooping cough to infants and the community.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.221-246
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• 1998

The aim of this experimental study was to evaluate the anti-tumor effects of Chungsimbohyeltang through investigation about viability of tumor cell by MTT assay, survival period of mice transplanted with L-1210 cells, growth inhibition on the tumor cell, body weight variation in mice transplanted with sarcoma-180 cells and its immunomodulatory effects through the investigation on delayed type hyper-sensitivity, the hemagglutinin and hemolysin titers for humoral immune response, the appearance of rosette forming cells for cell-mediated immune response, the natural killer cell activity, the transformation of lymphocyte, the productivity of Interleukin-2 and phagocytic index K was performed in immune-depressed ICR mice induced by methotrexate treatments. The results were as follows ; 1. $IC_{50}$ of Chungsimbohyeltang treated group was 5.85mg/ml in SNU-C4 cell, 1.38mg/ml in SNU-396 cell, 0.21mg/ml in SNU-1 cell, so it had low anti-tumor activity. 2. The both groups of Chungsimbohyeltang extract 10mg/kg and Chungsimbohyeltang extract 20mg/kg had no toxicity and the group of Chungsimbohyeltang 20mg/kg which was shown 120% in ILS had the effect of life prolongation in mice transplanted with L-1210 cells. 3. In the growth inhibition on the tumor cells, only the group of Chungsimbohyeltang extract 20mg/kg was noted and in the weight variation in mice transplanted with sarcoma-180 cells, both groups of Chungsimbohyeltang extract had a significant effect. 4. In the delayed type hypersensitivity and appearance of rosette forming cells, both groups of Chungsimbohyeltang extract didn't have any significant effect. 5. The hemagglutinin titers was slightly increased with no significance, and the hemolysin titers was significantly increased in the only group of Chungsimbohyeltang extract 20mg/kg. 6. The natural killer cell activity of the Chungsimbohyeltang extract groups was significantly increased in the ratio of 100:1 of effector and target cells, but it was not significantly increased in the ratio of 50:1, 10:1. 7. The transformation of lymphocyte and the productivity of Interleukin-2 were increased significantly and in dose-dependent manner in both group of Chungsimbohyeltang extract. 8. The phagocytic effect of macropage was significantly increased in both groups of Chungsimbohyeltang extract. Considering the results above, we could conclude that Chungsimbohyeltang have an indirect anti-tumor effect through the modulation of immunme response, although it had not toxicity on the tumor cell it self.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.8 no.1
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• pp.103-125
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• 2002

This experimental study was carried out to evaluate the anti-tumor and the immunomodulatory effects of Jiaweicitaowan(加未慈桃丸) against cancer. The in vitro anti-tumor effects were evaluated by MTT assay. The cytotoxicity, extension of survival days, the effect of inhibition solid tumor which was induced sarcoma 180, and the changes of body weight were evaluated for in vivo effects of anti-tumor. To evaluate the immunomodulatory effects of Jiawei- citaowan(加未慈桃丸), delayed type hypersensitivity, hemagglutinin, hemolysin titers for humoral immune response, rosette forming cells for cell-mediated immune response, natural killer cell activity, proliferation of lymphocyte, productivty of Interleukin-2, and carbon clearance were measured with methotrexate treated mice. The results were as follows; 1. In the case of existence ability of tumor cell, IC50 had an anti-tumor ativity resulted 2.52mg/ml to SNU-C4. 0.41mg/ml to SNU-396, resulted to 0.09mg/mlSNU-1. 2. The groups of Jiaweicitaowan(加未慈桃丸) 10mg/ml, 20mg/kg had no body weight loss. reduction in intake of water and feed, so these had no toxicity. 3. In the case of the effect of extention of existence. the group of 20mg/kg Jiaweicitaowan(加未慈桃丸) extract treated group was showed 250% in ILS. 4. The effect of inhibition solid tumor was significantly decreased in both 10mg/kg, 20mg/kg of Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group S. The groups of 10mg/kg, 20mg/kg Jiaweicitaowan(加未慈桃丸) had significant effect of body weight change compared to control group. 6. Delayed type hypersensitivity was not significant in both Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 7. Hemagglutinin and Hemolysin titers were significantly increased by dose-dependent. so these results showed that the humoral immume respose was activated. 8. For the effect of rosette formimg cells was not significant in hoth Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 9. Natural killer cell activity was significantly increased in both Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group in the ratio of 100: 1, 50: 1 of effector and target cells, but in the ratio of 10:1, the Jiaweicitaowan(加未慈桃丸) extract treated groups were not significant. 10. The proliferation of lymphocyte and productivty of Interleukin-2 were significantly increased by dose-dependent in both 10mg/ kg, 20mg/ kg of Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 11. In the phagocytic effect, the 20mg/kg of Jiaweicitaowan(加未慈桃丸) extract treated group showed the increasing effect with significance as compared with control group. According to the results, we can suggest that Jiaweicitaowan(加未慈桃丸) has the antitumor and the immunomodulatory effects.

• Journal of Microbiology and Biotechnology
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• v.32 no.1
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• pp.6-14
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• 2022

Brucella spp. are facultative intracellular pathogens that invade, survive and proliferate in numerous phagocytic and non-phagocytic cell types, thereby leading to human and animal brucellosis. Outer membrane proteins (Omps) are major immunogenic and protective antigens that are implicated in Brucella virulence. A strain deleted of the omp16 gene has not been obtained which suggests that the Omp16 protein is vital for Brucella survival. Nevertheless, we previously constructed an omp16 conditional deletion strain of Brucella, ∆Omp16. Here, the virulence and immune response elicted by this strain were assessed in a mouse model of infection. Splenomegaly was significantly reduced at two weeks post-infection in ∆Omp16-infected mice compared to infection with the parental strain. The bacterial load in the spleen also was significantly decreased at this post-infection time point in ∆Omp16-infected mice. Histopathological changes in the spleen were observed via hematoxylin-eosin staining and microscopic examination which showed that infection with the ∆Omp16 strain alleviated spleen histopathological alterations compared to mice infected with the parental strain. Moreover, the levels of humoral and cellular immunity were similar in both ∆Omp16-infected mice and parental strain-infected mice. The results overall show that the virulence of ∆Omp16 is attenuated markedly, but that the immune responses mediated by the deletion and parental strains in mice are indistinguishable. The data provide important insights that illuminate the pathogenic strategies adopted by Brucella.

• The Journal of the Korean Society for Microbiology
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• v.16 no.1
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• pp.49-55
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• 1981

Recent studies have demonstrated that histamine could have a modulatory influence on the immune response in vitro and in vivo. However, the effect of histamine on immune response in mice has not been extensivley analyzed. In the present study the regulatory effects of cimetidine, a histamine-2-receptor antagonist(H2 blocker) and histamine on the immune response to sheep red blood cells(SRBC) were evaluated in mice. Mice pretreated with daily intraperitoneal injection of varying concentrations of cimetidine for 14 days were immunized intraperitoneally with various concentrations of SRBC($10^6,\;10^7,\;and\;10^8$ cells) and challenged 4 days post immunization. The cellular immune response was determined by measuring the footpad swelling reaction. Footpad swelling reaction of each mouse was measured at 3hr(Arthus) reaction) and 24 or 48 hr(delayed reactions) after challenge. The humoral immune response was determined by measuring hemagglutinins to SRBC. Histamine in varying concentrations($10^{-1},\;10^{-3}\;and\;10^{-5}M$(was added in SRBC suspension at the time of antigen challenge into footpad, and 24-hr delayed type hypersensitivity(DTH) was measured. Cimetidine in varying concentrations(10, 50, 250, 1250 and 6250${\mu}g$) enhanced 24-hr DTH and this enhancement of DTH was more pronounced at 250${\mu}g$ of cimetidine. However, there were no significant differences between the cimetidine-pretreated groups and controls in Arthus reaction and hemagglutinin titers. Histamine suppressed the DTH in the dose-dependent fashion. This suppression was more pronounced at lower concentration of immunizing antigen($10^7\;and\;10^6$ SRBC). However, histamine did not diminish the DTH at higher concentration of antigen($10^8$ SRBC). These results present the evidences which strongly suggest that cimetidine enhances the cell-mediated immune response but not significantlly influences the humoral immune response and that exogenous and endogenous histamine is involved in the modulation of cellular immune response as well as immediate hypersensitivity.

• Journal of Life Science
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• v.24 no.2
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• pp.154-160
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• 2014

Ghost cells have been recognized as eliciting humoral and cell-mediated immune responses and have also been predicted to play a role as an immune adjuvant. In this study, we used the intramuscular (IM) route to inject BALB/c mice with four vaccine groups constructed from Salmonella typhimurium ghost (STG) cells originating from different virulent strains and complex STG groups instead of heat-labile toxin (LT)-B, a type of adjuvant. Although the complex STG groups exhibited a response after a short delay, the groups showed final total IgG levels similar to those of the LT-B group, which encodes LT-B from pMMP300. The IgG1 response to the ${\chi}$3339 group was the highest response at 6 weeks, whereas IgG2a responses to the ${\chi}$3339 and JOL389 groups were higher at 6 and 8 weeks compared to those of the LT-B group. The response of vaginal sIgA to the LT-B group was generally higher than that of the other groups, whereas fecal sIgA to the LT-B group exhibited lower responses. Protection to virulent S. typhimurium in all groups was above 80%, which was similar to the LT-B group. Taken together, we suggest that STG complex groups can be used as an immune adjuvant instead of LT-B.

• IMMUNE NETWORK
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• v.14 no.1
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• pp.21-29
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• 2014

Follicular helper T ($T_{FH}$) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, na$\ddot{i}$ve T cells are differentiating into $T_{FH}$ cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). $T_{FH}$ cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and $T_{FH}$ cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in $T_{FH}$ cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and $T_{FH}$ cell differentiation. $T_{FH}$ cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of $T_{FH}$ cells. The miR-17-92 cluster induces Bcl-6 and $T_{FH}$ cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T ($T_{FR}$) cells are studied as thymus-derived $CXCR5^+PD-1^+Foxp3^+\;T_{reg}$ cells that play a significant role in limiting the GC response. Regulation of $T_{FH}$ cell differentiation and the GC reaction via miRNA and $T_{FR}$ cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect $T_{FH}$ cell differentiation, and the role of $T_{FH}$ cells in autoimmune diseases.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.5
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• pp.723-731
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• 2008

Immunomodulatory feed additives might offer alternatives to antimicrobial growth promoters in pig production. This experiment was designed to determine the effects of dietary galacto-mannan-oligosaccharide (GMOS) and chitosan oligosaccharide (COS) supplementation on the immune response in early-weaned piglets. Forty 15-day-old piglets (Duroc$\times$Landrace$\times$Yorkshire) with an average live body weight of $5.6{\pm}0.51kg$ were weaned and randomly assigned to 4 treatment groups that were fed maize-soybean meal diets containing either basal, 110 mg/kg of lincomycin, 250 mg/kg of COS or 0.2% GMOS, respectively, over a 2-week period. Another six piglets of the same age were sacrificed on the same day at the beginning of the study for sampling, in order to obtain baseline values. Interleukin (IL)-1${\beta}$gene expression in peripheral blood monocytes, jejunal mucosa and lymph nodes, as well as serum levels of IL-1${\beta}$ IL-2 and IL-6, IgA, IgG, and IgM, were evaluated for 5 pigs from each group at 15 and 28 days of age. The results indicate that weaning stress resulted in decreases in serum antibody and cytokine levels. Dietary supplementation with GMOS or COS enhanced (p<0.05) IL-1${\beta}$gene expression in jejunal mucosa and lymph nodes, as well as serum levels of IL-1${\beta}$ IL-2, IL-6, IgA, IgG and IgM compared to supplementation with lincomycin. These findings suggest that GMOS or COS may enhance the cell-mediated immune response in early-weaned piglets by modulating the production of cytokines and antibodies, which shows that GMOS or COS have different effects than the antibiotic on animal growth and health.