• Archives of Pharmacal Research
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• v.25 no.6
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• pp.946-953
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• 2002

Bisphenol A [2, 2 bis (4-hydoxyphenyl) propane; BPA] is a widely used endocrine disruptors and has estrogenic: activities. Although interests on biological effect of BPA are rising, evidences of its effect on immune system are lacking. We investigated that the effect of BPA on immune parameters to postulate the mechanism, and BPA interruptions between neuroendocrine and immune system. BPA was administrated to mice by p.o. (as a drinking water) dose on 0.015, 1.5 and 30 mg/ml for 4 weeks. The BPA treatment did not result in any change in body weight, spleen weight and distribution of lymphocyte subpopulation collected from spleen. BPA induced prolactin production in spleen, and exposure of SPA increased the activity of splenocyte proliferation in response to Con A (p<0.001). The production of a strong Th-1 type cytokine ($IFN-{\gamma}$) was induced while Th-2 type (IL-4) was suppressed by SPA treatment. These were consistent with RT-PCR results of transcription factor GATA-3 and IRF-1. These findings suggested that stimulation of prolactin production by estrogenic effects of SPA would affect cytokine profiles, and lead to imbalanced cellular immune response. In addition, we could speculate that prolactin and cytokine is important mediator involved in network between neuroendocrine and immune system by BPA.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.88-88
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• 2020

Ginseng (Panax ginseng Meyer) is a very well-known traditional herbal medicine that has long been used to enhance the body's immunity. Because it is a type of ginseng, it is believed that wild simulated ginseng (WSG) also has immune-enhancing activity. However, study on the immune-enhancing activity of WSG is quite insufficient compared to ginseng. In this study, we evaluated immune-enhancing activity of WSG through macrophage activation to provide a scientific basis for the immune enhancing activity of WSG. WSG increased the production of immunomodulators such as NO, iNOS, COX-2, IL-1β, IL-6 and TNF-α and activated phagocytosis in mouse macrophages RAW264.7 cells. Inhibition of TLR2 and TLR4 reduced the production of immunomodulators induced by WSG. WSG activated MAPK, NF-κB and PI3K/AKT signaling pathways, and inhibition of such signaling activation blocked WSG-mediated production of immunomodulators. In addition, activation of MAPK, NF-κB and PI3K/AKT signaling pathways by WSG was reversed by TLR2 or TLR4 inhibition. Based on the results of this study, WSG is thought to activate macrophages through the production of immunomodulators and phagocytosis activation through TLR2/4-dependent MAPK, NF-κB and PI3K/AKT signaling pathways. Therefore, it is thought that WSG have the potential to be used as an agent for enhancing immunity.

• The Journal of Pediatrics of Korean Medicine
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• v.30 no.4
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• pp.29-59
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• 2016

Objectives PRAL (Prunus armeniaca Linne Var) has been known to suppress allergic reaction. However, the cellular target and its mechanism of action were unclear. This study was designed to investigate the effect of PRAL on RBL-2H3 mast cell, which is PMA-Ionomycin-induced activated in vitro and the effect of PRAL on the MNC/Nga mice that are DNCB-induced activated in vivo. Methods In this study, IL-4, IL-13 production were examined by ELISA analysis; IL-4, IL-13, IL-31, IL-31Ra, $TNF-{\alpha}$ and GM-CSF mRNA expression were examined by Real-time PCR; manifestations of AP-1 and MAPKs transcription factors were examined by western blotting in vitro. Then skin rashes have been evaluated and verified the distribution of mast cells by H&E and toluidine blue. Also, WBC, eosinophil and neutrophil, IgE level in serum, $IFN-{\gamma}$, IL-4, IL-5 in the splenocyte culture supernatant, the absolute cell numbers of $CD4^+$, $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$, $CD3^+CD69^+$ in the Axillary Lymph Node (ALN), PBMCs and dorsal skin and IL-5, IL-13, IL-31, IL-31Ra in the dorsal skin by Real-time PCR were all evaluated from the NC/BNga mice. Results As a result of this study, the mRNA expression of IL-4, IL-13, IL-31, IL-31Ra and $TNF-{\alpha}$ and IL-4, IL-13 production, shown in ELISA analysis, were suppressed by PRAL. Results from the western blot analysis showed decrease on the expression of mast-cell-specific transcription factors, including AP-1 and p-JNK, p-ERK. Histological examination showed that infiltration levels of immune cells in the skin of the AD-induced NC/Nga mice were improved by PRAL orally adminstration. Orally- administered PRAL group also showred decreased level of IgE in the serum. This group has shown decreased the level of IL-4, IL-5, but shown elevated $IFN-{\gamma}$ level in the splenocyte culture supernatant. The same group also has shown decreased cell numbers of $CD4^+$, $CD8^+$, $CD3^+CD69^+$ in the ALN, and $CD4^+$, $Gr-1^+CD11b^+$ in the dorsal skin. PRAL oral adminstration increased cell numbers of $CD4^+$, but decreased cell numbers of $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$ in the PBMCs. Conclusions Obtained results suggest that PRAL can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis (AD) induced in the NC/Nga mice. This may play an important role in recovering AD symptoms and suppressing pruritus.

• The Journal of Pediatrics of Korean Medicine
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• v.23 no.3
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• pp.9-36
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• 2009

Objectives The purpose of this study is to examine the effect of a concurrent administration of JUJSTK and AJ on atopic dermatitis in an in-vivo experiment. Thus, this study is expressed by using NC/Nga atopic dermatitis mice which have histological and clinical similarities to that of humans have been used. Methods Clinical skin score, hematology, serum total IgE and IgG1 of the mouse was evaluated, and cytokine levels, total number of the cells, immunohistochemical staining, histological features of axillary lymph node(ALN), peripheral blood mononuclear cells(PBMCs), and a dorsal skin tissue of the mouse were analyzed. Results Oral administration of JUJSTK and concurrent administration of JUJSTK and AJ lowered the clinical skin score, total cell number of WBC, eosinophils in blood, and serum total of IgE & IgG1, IFN-$\gamma$, IL-5, IL-13, IL-17. In addition, total cell number of ALN and dorsal skin tissue, absolute cell number of $CD3e^+$ T cell, $CD4^+$ Th cell, $CD8^+$ c/sT cell, $CD3^+CCR3^+$ cell, $CCR3^+$ cell, $CD3^+CD69^+$, $CD4^+CXCR5^+$ in ALN, PBMCs, absolute cell number of $CCR3^+$, $CD3^+/CD69^+$, $CD11b^+/Gr-1^+$, $CD11b^+/Gr-1^+$ in dorsal skin tissue, Eotaxin2 mRNA, CCR3 mRNA in dorsal skin tissue and gene expression of IL-5 mRNA, IL-13 mRNA in ALN were significantly decreased. Furthermore, thickness of epidermis infiltrated inflammatory immune cell & mast cell in dermis, histological infiltration of mast cell, the size of inflammatory lymphocytes cells & plasma cells in ALN and histological infiltration of $CD4^+$ & $CCR3^+$ in ALN and dorsal skin tissue were significantly decreased as well. Conclusions Concurrent administration of JUJSTK and AJ on atopic dermatitis in an in-vivoexperiment by using an NC/Nga atopic dermatitis mouse was very effective as an atopic dermatitis treatment.

• Biomedical Science Letters
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• v.2 no.2
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• pp.211-222
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• 1996

The conceptus which are resulted by mating between two genetically non-identical partners can be considered to be an allograft to the mother science which is not rejected by the mother's immunological attack. The present studies have been, therefore, attempted in order to elucidate the mechanism by which protection of the fete-placental allograft, between the C3H/HeJ female mouse and DBA/2 male mouse occurred. For this purpose, firstly systemic immunity was investigated by measuring T and B lymphocytes subsets. Natural killer cell activity in maternal splenic tissue and by observing the effects of pregnancy serums, progesterone and hCG on immune systems. Secondly, local immunity also investigated by measuring T lymphocytes subsets, natural killer cell activity in lymph nodes draining the uterus. The subsets of Thy-1.2$^+$ cells and L 3T4$^+$ cells decreased slightly while the subsets of Ly2$^+$ cell increased significantly compared with those of the control group beyond the mid-gestational stage. The subsets of B cell gradually in-creased from the mid-gestational stage untill delivery. The natural killer cell activity in the maternal splenic tissue significantly increased during the period of 5th to 8th day of gestation. The natural killer cell activity was significantly suppressed by the pregnancy serums and non-pregnant serums compared with those of serum-free group. The treatment of hCG significantly suppressed natural killer cell activity in the dose dependent manner (1 unit/ml-1000 unit/ml) while pro-gesterone increased the natural killer cell activity at phamarcological dose only. In the lymph nodes draining the uterus, the subsets of Thy-1.2$^+$ cells significantly increased during the period of implantation and L3T4$^+$ cell subsets slightly increased during the mid-gestational stage. The subsets of Ly2$^+$ cell increased significantly during the mid-gestational stage, but decreasing slightly be-fore delivery. The natural killer cell activity was significantly elevated after the implantation period in the lymph nodes draining the uterus. The natural killer cell activity of the lymph nodes draining the uterus was higher than those of splenic tissue during the same periods of gestation. It is therefore, concluded that during the pregnancy, the phenomena which the fete-placental allograft has not been rejected and rather protected from the maternal immunological attack might be due to local immune suppression in fete-maternal interface tissues rather than systemic immune suppression. And the subsets of Thy-1.2$^+$ cells and L3T4$^+$ cells mainly contribute to accepting allograft in early stage of pregnancy, while the subsets of Ly2$^+$ cell and the subsets of B cell increased significantly compared with those of the control group beyond the mid-gestational stage, so their role in systemic immunity and local immunity gradually increased from the mid-gestational stage until delivery.

• The Journal of Pediatrics of Korean Medicine
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• v.23 no.2
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• pp.51-85
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• 2009

Objectives : The purpose of this study is to investigate the effect of concurrent administration of KKSDU and AJ on atopic dermatitis in an in-vivo experiment using an NC/Nga atopic dermatitis mouse, which has histological and clinical similarities to the condition in humans. Methods : We evaluated clinical skin score, hematology, serum total IgE and IgG1 of NC/Nga atopic dermatitis mouse and analyzed the cytoline level, total cell number, immunohistochemical staining, histological features of axillary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue in NC/Nga mouse. Results : Orally administration of KKSDU and concurrent administration of KKSDU and AJ decreased the clinical skin score, total cell number of WBC, platelet, neutrophils, eosinophils in blood, serum total IgE & IgG1, IL-5, IL-13. Also, total cell number of ALN and dorsal skin tissue, absolute cell number of CD3e+&CD19+, CD4+&CD8+, CD3+/CCR3+, CCR3+, CD3+/CD69+, CD3+/CXCR5+ in ALN, PBMCs, absolute cell number of CCR3+, CD3+/CD69+, CD11b+/Gr-1+ in dorsal skin tissue, Eotaxin2 mRNA, CCR3 mRNA in dorsal skin tissue and gene expression of IL-5 mRNA, IL-13 mRNA in ALN are significantly decreased. Furthermore, thickness of epidermis, infiltrated inflammatory immune cell & mast cell in dermis, histologic infiltration of mast cell, the size of inflammatory lymphocytes cells & plasma cells in ALN and histologic infiltration of CD4+ & CCR3+ in ALN and dorsal skin tissue are significantly decreased. However, total cell number of DLN, absolute cell number of CD3+&CD19+, CD4+&CD8+, B220+/CD23+, CD3+/CD69+ in DLN and CD4+CD25+foxp3+Treg cell, foxp3 mRNA in dersal skin tissue are increased significantly. Conclusions : Concurrent administration of KKSDU and AJ on atopic dermatitis in an in-vivo experiment using an NC/Nga atopic dermatitis mouse was very effective to the atopic detmatitis treatment.

• The Journal of Pediatrics of Korean Medicine
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• v.23 no.1
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• pp.37-72
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• 2009

Objectives The purpose of this study is to investigate the suppressive effects of Atopy cream-combined with Jawoongo ointment (A-J), on the development of atopic dermatitis-like skinlesions in NC/Nga mouse. Methods We evaluated clinical skin score, hematology and Serum total IgE and IgG1 of NC/Nga atopic dermatitis mouse, analyzed the cytokine level, total cell number, Immunohistochemical staining and Histological features of axillary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue in NC/Nga mouse. Results A-J decreased the clinical skin score, total cell number of WBC, platelet, neutrophils, eosinophils in blood, Serum total IgE & IgG1, IL-5, IL-13. Also, total cell number of ALN and dorsal skin tissue, Absolute cell number of $CD3e^+$&$CD19^+$, $CD4^+$&$CD8^+$, $CD3^+/CCR3^+$, $CCR3^+$, $CD3^+/CD69^+$, $CD3^+/CXCR5^+$ in ALN, PBMCs, Absolute cell number of $CCR3^+$, $CD3^+/CD69^+$, $CD11b^+/Gr-1^+$ in dorsalskin tissue, Eotaxin2 mRNA, CCR3 mRNA in dorsal skin tissue and gene expression of IL-5 mRNA, IL-13 mRNA in ALN decreased significantly. Furthermore, thickness of epidermis, infiltrated inflammatory immune cell and mast cell in dermis, histologic infiltration of mast cell, the size of inflammatory lymphocytes cells and plasma cells in ALN and histologic infiltration of CD4+ & CCR3+ in ALN and dorsal skin tissue decreased significantly. However, total cell number of DLN, absolute cell number of $CD3e^+$&$CD19^+$, $CD4^+$&$CD8^+$, $B220^+/CD23^+$, $CD3^+/CD69^+$ increased significantly. Conclusions A-J was the successful treatment of atopic dermatitis in a NC/Nga mouse model.

• Korean Journal of Veterinary Research
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• v.36 no.4
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• pp.839-844
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• 1996

This study was designed to investigated the effects of cadmium(Cd) feeding on the humoral immune responses such as PFC-responses and production of immunoglobulins in BALB/c mice. The results obtained were summarized as follows; 1. Total PFCs of direct IgM antibody response were significantly decreased in all Cd-fed goups, whereas total PFCs of IgG antibody response were slightly increased. 2. In secondary immunization, total HA titers were increased in all Cd groups as compared with control, especially in 100ppmm group and also IgG titers were slightly increased except for 50ppm group. 3. The levels of $IgG_1$ were increased to 5.5% 18.7%, 17.4% and 7.2% in 25, 50, 100 and 200ppm groups as compared with control, respectively. And also the levels of IgE were increased to 5.7%, 7.3%, 8.7% and 0.4% in those of Cd groups, in order. Conclusively, concentrations of $IgG_1$, and IgE were increased in all Cd groups. Based on the results of this study and previous report, it was shown that Cd might affect humoral immune responses by modifying the distribution and function of cells playing in the cellular immune response.

• IMMUNE NETWORK
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• v.9 no.4
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• pp.133-137
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• 2009

We have recently shown that activin A, a member of TGF-$\beta$ superfamily, stimulates mouse B cells to express IgA isotype but other isotypes. In the present study, we further characterized effects of activin A on B cell growth and IgA expression. We found that activin A did not have effect on LPS-stimulated cell viability. In parallel, CFSE staining analysis revealed that activin A did not alter cell division. An increase of IgA secretion by activin A was completely abrogated by anti-activin A Ab but not by anti-TGF$\beta$1 Ab. In the same conditions, no other isotypes are significantly affected by each antibody treatment. Finally, activin A, as similar to TGF-$\beta$1, increased IgA secretion by mesenteric lymph node cells. These results suggest that activin A can specifically stimulate IgA response, independent of TGF-$\beta$ in the gut.

• Journal of Sasang Constitutional Medicine
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• v.15 no.2
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• pp.166-179
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• 2003

In order to evaluate the antiallergic effects of CSYJT, studies were done. We measured the cytotoxic activity for cytokines transcript expression, production of IL-4, IgE, $IFN-{\gamma}$, proliferation of B cell in HRF plus anti-CD40mAb plus rIL-4 stimulated murine splenic B cells. and cytokines transcript expression of IgE in Mast cell The results were obtained as follows: 1. CSYJT decreased the expression of IL-4 in mast cell significantly. 2. CSYJT decreased the production of IL-4 significantly. 3. CSYJT decreased the expression of IgE in mast cell significantly. 4. CSYJT decreased the production of IgE significantly. 5. CSYJT increased the appearance of $IFN-{\gamma}$. The facts above prove that CSYJT is effective against the allergy. Thus, I think that we should study on this continuously.