We investigated the immune enhancement effects of JaSaengHwan (JSH). The forced swimming test (FST) has been used as a screening model for new immune enhancement agents. We found that JSH (0.1 mg/ml) significantly reduced the immobility time in the FST compared to the control. Also, we investigated the effect of JSH on the proliferation of T cell and production of cytokines in human T-cell line, MOLT-4 cells and mouse peritoneal macrophages. JSH (1 mg/ml) significantly increased the cell proliferation by $46.78{\pm}6.41%$ (p<0.05) and also significantly increased the interleukin (IL)-2, IL-4 and interferon $(IFN)-{\gamma}$ production compared with media control (about 2-fold for IL-2, 3-fold for IL-4 and 1.5-fold for $IFN-{\gamma}$, p<0.05) at 24 h. In addition, JSH increased the production of IL-12 on the mouse peritoneal macrophages (by 3.6-fold for IL-12, p<0.05). In conclusion, these data indicate that JSH may have an immune-enhancement effect.
Even though appropriate immune response is necessary for the survival of the individual, excessive or insufficient immune Response might cause autoimmune or allergic disease. So the immune response must be controlled to the degree that is beneficial for the well being of the individual. This study was undertaken to know the effects of Gunleetang Gagambang on the immune system of the mouse. Gunleetang Gagambang has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carried out to evaluate the possible therapeutic or antitumoral effects of Gunleetang Gagambang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene(MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S180 cells). Treatment of the Gunleetang Gagambang on water-extract(dailly 1mg/mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Gunleetang Gagambang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice(TBM). Gunleetang Gagambang on also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurrence-frequency and their size. and some developed tumors were regressed by the continuous treatment of Gunleetang Gagambang extract into TBM. In vitro, treatment of Gunleetang Gagambang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Gunleetang Gagambang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Gunleetang Gagambang administration to mice enhanced NK cells activities. These results demonstrated that Gunleetang Gagambang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Gunleetang Gagambang might be chiefly due to nonspecitie enhancement of NK cell activities and cell-mediated immune responses.
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.
A protein-polysaccharide fraction of a Korean wild mushroom Psathyrella velutina, PVP, was prepared and its antitumor immunomodulatory activity was investigated. When PVP was administered once daily for seven days from day 1 to day 7 into male ICR mice implanted with 1 $\times$ 10$^{5}$ cells of sarcom 180 tumor cells into the peritoneum on day 4, it inhibited the growth of sarcoma 180 cells by 92.8%. In XTT assay, PVP also exhorted in vitro anti-proliferation activity on U-937, a human monoblastoid cell line, as well as sarcoma 180 cells. PVP showed marked stimulatory activity on the immune system in that it induced the accumulation of PEC (the stimulation index, Sl=4.90 at 100 mg/kg), stimulated the BALB/c mouse splenic lymphocytes to form lymphoblasts (Sl=5.75 at 100$\mu\textrm{g}$/ml), and upergulated the expression of CD25 molecules. All these results strongly support that PVP exhorts its antitumor activity through stimulation of the immune system as well as anti-proliferative activity on the tumor cells.
Natural products are increasingly appreciated as a lead for drug discovery and development. A number of investigators have studied various activities of natural products and have found that they have not only nutritional effects but also beneficial properties to cure various diseases and to maintain good health. Job's Tear(Yul-Moo) is a grass crop that have long been used in traditional medicine and a nourishing food. Job's Tear has been reported to exhibit anti-inflammatory, stomachic, antiallergic activity, and antispastic effects and has been used in China for the treatment of warts, rheumatism, and neuralgia although its mechanism remains unclear. Previous results in our laboratory demonstrated that the ethanol extract and water extract of Job's Tear exerted an immune regulatory function on mice cells in vitro. The present study was performed to investigate the ex vivo effect of Job's Tear on immune function. Seven to eight weeks old mices(Balb/c) were fed ad libitum on chow diet and water extract of Job's Tear were orally administrated every other day for two or four weeks at two different concentrations (50 and 500mg/kg B.W.). Proliferation of mice spenocytes and antibody production to sheep red blood cells(SRBC) using hemolytic plague forming cell assay were used to indicate the immune activity. Splenocytes proliferation of Job's Tear with mitogen stimulation such as Con A and LPS was enhanced at 50 mg/kg B.W. concentrations compared to those of control group. In case of antibody production to sheep red blood cells, the number of antibody- secreting cells was increased by administration of 50mg/kg B.W. concentration in mice immunized as a T-dependent antigen. From the present study, Job's Tear water extracts may be suggested to stimulate the mice immune response by enhancing the splenocytes proliferation and the number of plague forming cells.
Objectives: This study was designed to investigate the anti-tumor metastasis by anti-inflammatory and innate immunomodulating effects of extracts of Jipae-san on cancer cells. Methods: Antimetastatic experiments were conducted in vivo mouse model by using 4T1 mouse mammary carcinoma cells. Cell viability of Jipae-san was tested with 4T1 mouse mammary carcinoma cells, colon 26-M3.1 carcinoma cells and macrophage. In addition expression of $TNF-{\alpha}$ and NO induced by LPS was measured after treating with Jipae-san. To observe innate immunomodulating effects of Jipae-san on macrophage, we measured $TNF-{\alpha}$, IL-12, IL-6 and MCP-1, respectively. Cell cytotoxicity was tested with the macrophage stimulated with Jipae-san and we evaluated the activation of $TNF-{\alpha}$ and NO. And the effect of Jipae-san on metastasis was measured without NK-cell using GM1 serum. Results: Intravenous inoculation of Jipae-san significantly inhibited metastasis of 4T1 mouse mammary carcinoma cells. In an in vitro cytotoxicity analysis, cell growth are closer to 100% less than $1,000{\mu}g/ml$ concentration. The expression of $TNF-{\alpha}$ and NO induced by LPS after treating Jipae-san was down regulated in dose-dependent manner. Level of cytokines such as $TNF-{\alpha}$, IL-12, IL-6 and MCP-1 of Jipae-san group were up regulated in compared to the control group. The macrophage stimulated with Jipae-san significantly inhibits the cancer cell at ratio of 10:1, 20:1. The activation of NO was significantly up regualted in a group of 5:1, 10:1, 20:1. The depletion of NK-cells by anti-asialo GM1 serum partly abolished the inhibitory effect of Jipae-san on tumor metastasis. Conclusions: Jipae-san appears to have considerable activity on the anti-metastasis by inflammation control and activation of innate immune system.
Ji Hwa Hong;Sang Hoon Kim;Hyun Gyung Kim;Jun Ho Jang;Ryeo Gang Son;Seung Pil Pack;Young-Ho Park;Philyong Kang;Kang-Jin Jeong;Ji-Su Kim;Hanbyeul Choi;Sun-Uk Kim;Yong Woo Jung
IMMUNE NETWORK
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v.21
no.3
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pp.24.1-24.13
/
2021
Due to the inconsistent fluctuation of blood supply for transfusion, much attention has been paid to the development of artificial blood using other animals. Although mini-pigs are candidate animals, contamination of mini-pig T cells in artificial blood may cause a major safety concern. Therefore, it is important to analyze the cross-reactivity of IL-7, the major survival factor for T lymphocytes, between human, mouse, and mini-pig. Thus, we compared the protein sequences of IL-7 and found that porcine IL-7 was evolutionarily different from human IL-7. We also observed that when porcine T cells were cultured with either human or mouse IL-7, these cells did not increase the survival or proliferation compared to negative controls. These results suggest that porcine T cells do not recognize human or mouse IL-7 as their survival factor.
The periodontal diseases are infections caused by bacteria in oral biofilm, a gelatinous mat commonly called dental plaque, which is a complex microbial community that forms and adhere to tooth surfaces. Host immune-pathogen interaction in periodontal disease appears to be a complex process, which is regulated not only by the acquired immunity to deal with ever-growing and -invading microorganisms in periodontal pockets, but also by genetic and/or environmental factors. However, our understanding of the pathogenesis in human periodontal diseases is limited by the lack of specific and sensitive tools or models to study the complex microbial challenges and their interactions with the host's immune system. Recent advances in cellular and molecular biology research have demonstrated the importance of the acquired immune system in fighting the virulent periodontal pathogens and in protecting the host from developing further devastating conditions in periodontal infections. The use of genetic knockout and immunodeficient mouse strains has shown that the acquired immune response, in particular, $CD4^+$ T-cells plays a pivotal role in controlling the ongoing infection, the immune/inflammatory responses, and the subsequent host's tissue destruction.
Bikiwhan is one of the oriental medicines that have been used for the treatment of tumors since ancient times. However, the mechanism of the drug action is not closely surved. This study was made to investigate the effects of Bikiwhan on the innate immunity were analysed by measuring the functions of phagocytes, and those of specific immunity were analysed by measuring T and B cells activities. The followings are the results obtained from this study : 1. Bikiwhan has direct cytotoxic effects against human lymphoma cell lines (K562) in a dose dependent manner. 2. An administration of Bikiwhan increased allogenic immune response in the mouse. 3. An administration of Bikiwhan increased the antibodies formation against SRBC. 4. An administration of Bikiwhan enhanced the apperance of rosette forming cells in the spleen. 5. An administration of Bikiwhan decreased the delayed-type hypersensitivity against dinitrofluorobenzene. 6. An administration of Bikiwhan has no effect on natural killer cells. 7. Bikiwhan increased the phagocyte activity of peritoneal macrophages in vitro and in in vivo as well. 8. Bikiwhan depressed the formation of reactive oxygen intermediated in vitro and in vivo as well. 9. Bikiwhan has the capacity to make peritoneal macrophages secrete nitric oxide. The above results demonstrate that Bikiwhan has enhancing effects of immune responses against tumors by decreasing tissue demages caused by immune responses.
Innate lymphoid cells (ILCs) are critical immune-response mediators. Although they largely reside in mucosal tissues, the kidney also bears substantial numbers. Nevertheless, kidney ILC biology is poorly understood. BALB/c and C57BL/6 mice are known to display type-2 and type-1 skewed immune responses, respectively, but it is unclear whether this extends to ILCs. We show here that indeed, BALB/c mice have higher total ILCs in the kidney than C57BL/6 mice. This difference was particularly pronounced for ILC2s. We then showed that three factors contributed to the higher ILC2s in the BALB/c kidney. First, BALB/c mice demonstrated higher numbers of ILC precursors in the bone marrow. Second, transcriptome analysis showed that compared to C57BL/6 kidneys, the BALB/c kidneys associated with significantly higher IL-2 responses. Quantitative RT-PCR also showed that compared to C57BL/6 kidneys, the BALB/c kidneys expressed higher levels of IL-2 and other cytokines known to promote ILC2 proliferation and/or survival (IL-7, IL-33, and thymic stromal lymphopoietin). Third, the BALB/c kidney ILC2s may be more sensitive to the environmental signals than C57BL/6 kidney ILC2s since they expressed their transcription factor GATA3 and the IL-2, IL-7, and IL-25 receptors at higher levels. Indeed, they also demonstrated greater responsiveness to IL-2 than C57BL/6 kidney ILC2s, as shown by their greater STAT5 phosphorylation levels after culture with IL-2. Thus, this study demonstrates previously unknown properties of kidney ILC2s. It also shows the impact of mouse strain background on ILC2 behavior, which should be considered when conducting research on immune diseases with experimental mouse models.
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