• Radiation Oncology Journal
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• v.25 no.3
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• pp.185-191
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• 2007

Purpose: This study was performed to investigate the effects of immune cell activation and the antitumor effect for the combination of treatment with X-irradiation and E/eutherococcus senticosus Maxim Root (ESMR) on mouse tumor cells. Materials and Methods: ESMR (250g) was extracted with 80% methanol, concentrated under decompression and lyophilized. To determine whether ESMR is able to activate the immune cells or not, the proliferation of splenocytes in vitro and the number of B cells and T cells in splenic lymphocytes in ESMR-pretreated mice were evaluated. X-irradiation was given to the mouse fibrosarcoma tumor cells (FSa II) by 250 kv X-irradiation machine. The cytotoxicity of ESMR was evaluated from its ability to reduce the clonogenecity of FSa II cells. In X-irradiation alone group, each 2, 4, 6 and 8 Gy was given to FSa II cells. In X-irradiation with ESMR group, 0.2 mg/ml of ESMR was exposed to FSa II cells for 1 hour before X-irradiation. Results: The proliferation of cultured mouse splenocytes and thymocytes were enhanced by the addition of ESMR in vitro. The number of B cells and T cells in mouse splenic lymphocytes was significantly increased in ESMR pretreated mice in vivo. In FSa II cells that received a combination of 0.2 mg/ml of ESMR with X-irradiation exposure, the survival fraction with a dose of 2, 4 and 6 Gy was $0.39{\pm}0.005$, $0.22{\pm}0.005$ and $0.06{\pm}0.007$, respectively. For FSa II cells treated with X-irradiation alone, the survival fraction with a dose of 2, 4 and 6 Gy was $0.76{\pm}0.02$, $0.47{\pm}0.008$ and $0.37{\pm}0.01$. The difference in the survival fraction of the mouse FSa II cells treated with and without ESMR was statistically significant (p<0.05). Conclusion: Treatment with ESMR increased cell viability of mouse splenocytes in vitro and especially the subpopulation of B cells and T cells in splenocytes in ESMR-pretreated mice. However, treatment with ESMR did not increase the level of Th and Tc subpopulations in the thymocytes. Treatment with the combination of ESMR and X-irradiation was more cytotoxic to mouse tumor cells than treatment with X-irradiation alone; this finding was statistically significant.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.136-144
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• 2007

Biotae Orientalis has been widely used for treatment of relaxion of smooth muscle, gastrointestinal hemorrhage and alopecia in Oriental Medicine. This experiment examined the effect of an extracts, obtained from the acetone and MeOH extracts of dried or fresh Biotae Orientalis, on hair growing activity of the C57BL/6N mice after topical application to skin. First, We examined on hair growth activity of extracts of Biotae Orientalis compare to control and 1% minoxidil groups. Second, We investigated on the number of hair follicle and mast cells after topical application of extracts of the Biotae Orientalis to skin for 16 day. Third, We investigated immunoreactive density of vascular endothelial growth factor(VEGF), protein kinase C-${\alpha}$(PKC-${\alpha}$) and stem(mast) cell factor(SCF) in skin of C57BL/6N mice by immunohistochemical methods. I fourth investigated changes of subpopulation of splenocytes and thymocytes in C57BL/6N mice for 16day using laser flow cytometry. The results were as follows : Hair growing effect of acetone and MeOH extracts of dried and fresh Biotae Orientalis was observed in 70%, 90% and 60% in hair removed skin area in 16 day respectively. Immunoreactive density of VEGF and PKC-${\alpha}$ in skin of experimental groups was weakly stained compare to control group in 10 day. Immunoreactive density of stem cell factor in skin of experimental group was heavily stained compare to control group in 10 day. Splenic TH/TC Iymphocytes of lived MeOH extracts group significantly increased compare to control group. TH cells in thymic T lymphocytes were increased compare to control group. These experiment suggest that acetone and MeOH extracts of Biotae Orientalis may be used for topical treatment of alopecia areata.

• Toxicological Research
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• v.26 no.4
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• pp.261-266
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• 2010

In the workplace, the arsenic is used in the semiconductor production and the manufacturing of pigments, glass, pesticides and fungicides. Therefore, workers may be exposed to airborne arsenic during its use in manufacturing. The purpose of this study was to evaluate the potential toxicity of particulate matters (PMs) doped with arsenic (PMs-Arsenic) using a rodent model and to compare the genotoxicity in various concentrations and to examine the role of PMs-Arsenic in the induction of signaling pathway in the lung. Mice were exposed to PMs $124.4{\pm}24.5\;{\mu}g/m^3$ (low concentration), $220.2{\pm}34.5\;{\mu}g/m^3$ (middle concentration), $426.4{\pm}40.3\;{\mu}g/m^3$ (high concentration) doped with arsenic $1.4\;{\mu}g/m^3$ (Low concentration), $2.5\;{\mu}g/m^3$ (middle concentration), $5.7\;{\mu}g/m^3$ (high concentration) for 4 wks (6 h/d, 5 d/wk), respectively in the whole-body inhalation exposure chambers. To determine the level of genotoxicity, Chromosomal aberration (CA) assay in splenic lymphocytes and Supravital micronucleus (SMN) assay were performed. Then, signal pathway in the lung was analyzed. In the genotoxicity experiments, the increases of aberrant cells were concentration-dependent. Also, PMs-arsenic caused peripheral blood micronucleus frequency at high concentration. The inhalation of PMs-Arsenic increased an expression of phosphorylated Akt (p-Akt: protein kinase B) and phpsphorylated mammalian target of rapamycin (p-mTOR) at high concentration group. Taken together, inhaled PMs-Arsenic caused genotoxicity and altered Akt signaling pathway in the lung. Therefore, the inhalation of PMs-Arsenic needs for a careful risk assessment in the workplace.

• Molecules and Cells
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• v.38 no.11
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• pp.966-974
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• 2015

Despite the presence of toll like receptor (TLR) expression in conventional $TCR{\alpha}{\beta}$ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 ($H-2^b$) ${\rightarrow}$ B6D2F1 ($H-2^{b/d}$), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type ($H-2^d$) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-${\gamma}$ or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-${\gamma}$ producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT.

• Journal of Microbiology and Biotechnology
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• v.31 no.5
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• pp.667-675
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• 2021

Streptococcus agalactiae is an important bacterial pathogen and causative agent of diseases including neonatal sepsis and meningitis, as well as infections in healthy adults and pregnant women. Although antibiotic treatments effectively relieve symptoms, the emergence and transmission of multidrug-resistant strains indicate the need for an effective immunotherapy. Effector T helper (Th) 17 cells are a relatively newly discovered subpopulation of helper CD4⁺ T lymphocytes, and which, by expressing interleukin (IL)-17A, play crucial roles in host defenses against a variety of pathogens, including bacteria and viruses. However, whether S. agalactiae infection can induce the differentiation of CD4⁺ T cells into Th17 cells, and whether IL-17A can play an effective role against S. agalactiae infections, are still unclear. In this study, we analyzed the responses of CD4⁺ T cells and their defensive effects after S. agalactiae infection. The results showed that S. agalactiae infection induces not only the formation of Th1 cells expressing interferon (IFN)-γ, but also the differentiation of mouse splenic CD4⁺ T cells into Th17 cells, which highly express IL-17A. In addition, the bacterial load of S. agalactiae was significantly increased and decreased in organs as determined by antibody neutralization and IL-17A addition experiments, respectively. The results confirmed that IL-17A is required by the host to defend against S. agalactiae and that it plays an important role in effectively eliminating S. agalactiae. Our findings therefore prompt us to adopt effective methods to regulate the expression of IL-17A as a potent strategy for the prevention and treatment of S. agalactiae infection.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.43.1-43.11
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• 2020

Capicua (CIC) is a transcriptional repressor that regulates several developmental processes. CIC deficiency results in lymphoproliferative autoimmunity accompanied by expansion of CD44^hiCD62L^lo effector/memory and follicular Th cell populations. Deletion of Cic alleles in hematopoietic stem cells (Vav1-Cre-mediated knockout of Cic) causes more severe autoimmunity than that caused by the knockout of Cic in CD4⁺CD8⁺ double positive thymocytes (Cd4-Cre-mediated knockout of Cic). In this study, we compared splenic CD4⁺ T cell activation and proliferation between whole immune cell-specific Cic-null (Cic^f/f;Vav1-Cre) and T cell-specific Cic-null (Cic^f/f;Cd4-Cre) mice. Hyperactivation and hyperproliferation of CD4⁺ T cells were more apparent in Cic^f/f;Vav1-Cre mice than in Cic^f/f;Cd4-Cre mice. Cic^f/f;Vav1-Cre CD4⁺ T cells more rapidly proliferated and secreted larger amounts of IL-2 upon TCR stimulation than did Cic^f/f;Cd4-Cre CD4⁺ T cells, while the TCR stimulation-induced activation of the TCR signaling cascade and calcium flux were comparable between them. Mixed wild-type and Cic^f/f;Vav1-Cre bone marrow chimeras also exhibited more apparent hyperactivation and hyperproliferation of Cic-deficient CD4⁺ T cells than did mixed wild-type and Cic^f/f;Cd4-Cre bone marrow chimeras. Taken together, our data demonstrate that CIC deficiency at the beginning of T cell development endows peripheral CD4⁺ T cells with enhanced T cell activation and proliferative capability.