• Title/Summary/Keyword: IFN-$\gamma$

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Chitinase 3-like-1, a novel regulator of Th1/CTL responses, as a therapeutic target for increasing anti-tumor immunity

  • Kim, Do-Hyun;Choi, Je-Min
    • BMB Reports
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    • v.51 no.5
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    • pp.207-208
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    • 2018
  • Chitinase-Like Proteins (CLPs) are an evolutionarily conserved protein which lose their enzymatic activity for degrading chitin macromolecules. Chitinase-3-like-1 (Chi3l1) is a type of CLP that is highly expressed in epithelial cells, macrophages, etc., and is known to have correlations with type 2 inflammation and cancer. Although the increased level of Chi3l1 in the blood was reported in various disease patients, the function of Chi3l1 in adaptive immunity has been totally unknown. Recently, we found that Chi3l1 is expressed in T cells and has a negative regulatory role in T-cell activation and proliferation. A genetic ablation study of Chi3l1 in T cells showed hyperresponsiveness to TcR stimulation, which increased proliferation and Th1 differentiation. A significant increase of $IFN{\gamma}$ signaling in Chi3l1-deficient T cells synergistically increased Th1 and CTL functions against melanoma cells in vitro and in vivo. In addition, targeted knockdown by Chi3l1 siRNA complexed with the cell-penetrating peptide dNP2, which showed decreased pulmonary melanoma metastasis with increased infiltration of Th1 and CTL in the lung. This study first suggests that Chi3l1 is a novel regulator of Th1/CTL responses and could be a target for treating cancer to increase tumor immunity.

Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway

  • Kim, Eun Jeong;Kim, Jeeho;Lee, Min Young;Sudhanva, Muddenahalli Srinivasa;Devakumar, Sundaravinayagam;Jeon, Young Jin
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.282-287
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    • 2014
  • We show that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibits cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced production of nitric oxide (NO) in the pancreatic beta cell line MIN6N8a. Immunostaining and Western blot analysis showed that silymarin inhibits iNOS gene expression. RT-PCR showed that silymarin inhibits iNOS gene expression in a dose-dependent manner. We also showed that silymarin inhibits extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) phosphorylation. A MEK1 inhibitor abrogated CM-induced nitrite production, similar to silymarin. Treatment of MIN6N8a cells with silymarin also inhibited CM-stimulated activation of NF-${\kappa}B$, which is important for iNOS transcription. Collectively, we demonstrate that silymarin inhibits NO production in pancreatic beta cells, and silymarin may represent a useful anti-diabetic agent.

Effect of Water Extracts from Root of Taraxacum officinale on Innate and Adaptive Immune Responses in Mice (민들레 뿌리 물 추출물의 마우스 선천 및 획득 면역계에 미치는 효과)

  • Yoon, Taek-Joon
    • The Korean Journal of Food And Nutrition
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    • v.21 no.3
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    • pp.275-282
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    • 2008
  • Hot-water($100^{\circ}C$) and cold-water($4^{\circ}C$) extracts of Taraxacum officinale root were assessed for the effects of innate and adaptive immune responses in mice. Hot water extracts(TO-100) and cold water extracts(TO-4) did not affect the viability of macrophages at concentrations below to 18 mg/ml and 8 mg/ml, respectively. The thioglycollate-induced macrophages cultured with TO-100 and TO-4 produced a significantly higher quantity of various cytokines, such as IL-6 and IL-12, than those treated with medium. This shows that the extracts potently stimulated the innate immune response. When mice were subcutaneously immunized(sc) with OVA+FIA(Freund's incomplete adjuvant)-emulsified TO-100, TO-100 did not affect the production of IgE, but enhanced the production of IgG1, IgG2a and IgG2b. The culture supernatant obtained from the splenocytes of mice treated with OVA+FIA-emulsified TO-100 also evidenced elevated levels of both OVA-specific Th1-type(IFN-$\gamma$) and Th2-type cytokines(IL-4, IL-6 and IL-10). These results suggested that TO-100 can modulate the immune responses to allergens in mice.

Development and Evaluation of the Psychosocial Distress Nursing Intervention for Patients with Gynecological Cancer (디스트레스 간호중재가 부인암 환자의 디스트레스, 면역 및 삶의 질에 미치는 효과)

  • Park, Jeong-Sook;Oh, Yun-Jung
    • Korean Journal of Adult Nursing
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    • v.24 no.3
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    • pp.219-231
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    • 2012
  • Purpose: The purpose of this research was to develop and evaluate a distress nursing intervention for relieving psychosocial distress. Methods: We developed a twelve-week non-pharmacological distress nursing intervention to decrease distress. This intervention includes cognitive behavioral therapy, mindfulness based stress reduction, psychoeducation and supportive therapy. The participants were 27 gynecologic cancer patients who agreed to participate in this study, selected by convenience sampling (experimental group-17 and control group-10). The data collection period was performed from November, 8, 2010 to February, 1, 2011. Data were analyzed by using the SPSS/WIN 18.0 program. Results: There were no difference between the two groups distress score, distress problem and quality of life. The experimental group had significant higher IL-12 and IFN-${\gamma}$ and lower TGF-${\beta}$ between before and after the distress nursing intervention. Conclusion: The findings indicate that the distress nursing intervention was an effective intervention in improving immunologic function of gynecological cancer patients.

Immunomodulatory Activity of Pine Needle (Pinus densiflora) Extracts in Macrophages

  • Choi, Hye-Sook;Hang, Do;Cho, Seong-Jun;Kang, Se-Chan;Sohn, Eun-Soo;Lee, Sang-Pil;Pyo, Suhk-Neung;Son, Eun-Wha
    • Preventive Nutrition and Food Science
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    • v.11 no.2
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    • pp.105-109
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    • 2006
  • Pinus densiflora belongs to the Pinaceae family which has been widely used for health promoting purposes as folk medicine or as a food. Various curative effects of different parts of the pine have been reported including as a remedy for carcinoma. We examined the effects of pine needle water extracts (PNE) on macrophage function using peritoneal macrophage, pre-osteoclast bone macrophage (Raw 264.7 cell) and brain macrophage (C6 microglia). When peritoneal macrophages were treated with various concentrations of PNE ($1{\sim}100{\mu}g/mL$) for 24 hours, phagocytic activity was significantly increased, whereas it had no effect on tumoricidal activity and NO production. However, the treatment of Raw 264.7 with PNE resulted in the enhancement of NO production at high concentration ($100{\mu}g/mL$). Furthermore, the treatment of C6 with PNE increased the production of NO in a concentration-dependent manner, whereas PNE suppressed NO production in $LPS/IFN-{\gamma}-stimulated$ microglia. These results suggest that PNE has differential immunomodulatory effects on macrophages.

Rhei Rhizoma Extracts Have Antiproliferative Properties and Differential Effects on NO Production in Macrophages

  • Pyo, Suh-Kneung;Son, Eun-Wha
    • Preventive Nutrition and Food Science
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    • v.11 no.4
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    • pp.273-277
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    • 2006
  • Recently, Rhei Rhizoma extracts (RRE) have begun to receive more attention as potential biological response modifiers. In the present study, we studied the antiproliferative effect of RRE on tumor cells and the effect of RRE on macrophage function. A variety of tumor cells and macrophages were treated with RRE at various concentrations. The effect of RRE on cell proliferation was measured by MTT assay and the effect of RRE on the production of nitric oxide (NO) was determined in the macrophage-like cell lines Raw264.7, C6 and peritoneal macrophages (pMQ). RRE inhibited the growth of tumor cells (e.g., B16, HOS). However, the effects of RRE on the production of NO varied with macrophage types. RRE had no effect on C6 cell growth and slightly increased the growth of Raw264.7 cells. In addition, treatment of normal pMQ with RRE enhanced NO production in a concentration-dependent manner, whereas RRE suppressed NO production at $50\;{\mu}g/mL$ in both Raw264.7 and C6 cells. However, RRE suppressed NO production in LPS/IFN-$\gamma$-stimulated C6 cells. Overall, these results suggest that RRE elicits an antiproliferative property and differentially modulates NO production in various macrophages, and have a potential for therapeutic application.

Induction of 90K-specific Cytotoxic T Lymphocytes for Colon Cancer Immunotherapy

  • Lee, Ji-Hee;Park, Myung-Suk;Chung, Ik-Joo
    • IMMUNE NETWORK
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    • v.10 no.6
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    • pp.206-211
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    • 2010
  • Background: Dendritic cell (DC)-based tumor vaccine is an attractive modality for the treatment of colon cancer because it has been recurred and produced few side effects in patients. Secretory glycoprotein 90K has been found at elevated level in various cancer tissues and sera. We investigated to establish a more effective DC vaccine for the treatment of colon cancer in which the levels of 90K are elevated. Methods: We obtained the concentrated 90K from 293T cells stably expressing 90K. DCs were cultured from peripheral blood monocytes, and a DC vaccine pulsed with tumor lysate was compared with a DC vaccine pulsed with 90K. We measured the functional activity for CTLs by using IFN-${\gamma}$-enzyme linked immunoabsorbent spot (ELISPOT) assay. Results: DCs pulsed with tumor lysate+90K exhibited the enhanced T cell stimulation, polarization of $\ddot{i}$ T cell toward Th1. The CTLs generated by DCs pulsed with 90K efficiently lysed HCT116 cells. The results indicate that 90K-speicifc-CTLs can recognize 90K proteins naturally presented by colon cancer cells. Conclusion: Our study suggests that 90K-specific CTLs generated by 90K-pulsed DCs could be useful effector cells for immunotherapy in colon cancer.

Mistletoe Lectin (Viscum album coloratum) Modulates Proliferation and Cytokine Expressions in Murine Splenocytes

  • Lyu, Su-Yun;Park, Won-Bong
    • BMB Reports
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    • v.39 no.6
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    • pp.662-670
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    • 2006
  • It is well documented that an extract of European mistletoe has a variety of biological effects, such as the stimulation of cytokine production from immune cells, and additional immunoadjuvant activities. While the European mistletoe has been studied intensively, we know less about Korean mistletoe as a therapeutic plant, especially as a possible immunomodulating drug. This study will investigated the effects of Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) on murine splenocytes to investigate whether VCA acts as an immunomodulator, which could lead to improved immune responses in these cells. The results showed that VCA inhibited cell proliferation at higher concentrations (at 1-8 ng/ml) and enhanced cell proliferation at lower concentrations (at 4-32 pg/ml). Further studies were carried out to determine if the pro-proliferative or anti-proliferative activity exhibited by VCA was correlated with cytokine secretion. Consequently, interferon (IFN)-$\gamma$ secretion was decreased in concanavalin A (ConA)-stimulated murine splenocytes by VCA (4-64 ng/ml), but there was no change in IL-4 levels. This suggests that VCA has the ability to modulate murine splenocyte proliferation and can possibly act on the balance of Th1/Th2 cellular immune responses.

Effects of the water of yellow soil, Ji-Jang-Soo on cell viability and cytokines production in immune cells

  • Jeong, Hyun-Ja;Hwang, Gab-Soo;Myung, No-Il;Lee, Joon-Ho;Lee, Ju-Young;Um, Jae-Young;Kim, Hyung-Min;Hong, Seung-Heon
    • Advances in Traditional Medicine
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    • v.6 no.1
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    • pp.39-44
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    • 2006
  • Ji-Jang-Soo (JJS) is known to have a detoxification effect. However, it is still unclear how JJS has these effects in experimental models. In this study, we investigated the effect of JJS on the viability of cells and production of cytokines in human T-cell line, MOLT-4 cells, and human mast cell line, HMC-1 cells. The MOLT-4 cells were cultured for 24 h in the presence or absence of JJS. As the result, JJS (1/100 dilution) significantly increased the cell viability about 78% (P < 0.05) and also increased the interleukin (IL)-2, and interferon $(IFN)-{\gamma}$ production compared with media control at 24 h. But had no effect on IL-4 production. Hypoxia mimic compound, desferroxamine (DFX) decreased the immune cell viability. Cell viability decreased by DFX was increased by JJS. In conclusion, these data indicate that JJS may have an immune-enhancing effect.

Effects of Vitex rotundifolia on radical scavenging and nitric oxide production

  • Choi, Jae-Ki;Cha, Dong-Seok;Lee, Yong-Jae;Ko, Sung-Hoon;Park, Ho-Jun;Lee, Se-Yeoun;Choi, Jae-Hyuk;Jeon, Hoon
    • Advances in Traditional Medicine
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    • v.10 no.2
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    • pp.51-58
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    • 2010
  • Vitex rotundifolia (V. rotundifolia) has been used for treating headache, dizziness, toothache and removal of fever as a traditional medicine in Korea. In the present study, we examined the antioxidant and anti-inflammatory activities of 85% methanol extract of V. rotundifolia. In various radical scavenging assays, V. rotundifolia exhibited strong scavenging effect on 1, 1-diphenyl-2-picrylhydrazyl free radical, superoxide radical, nitric oxide. To elucidate the anti-inflammatory properties of V. rotundifolia, we investigated the inhibition effects of nitric oxide production in IFN-gamma and LPS-stimulated mouse peritoneal macrophages. V. rotundifolia suppressed nitric oxide production, iNOS and COX-2 expression dose-dependently through suppression of NF-$\hat{e}B$ activation without notable cytotoxicity. These findings mean that V. rotundifolia may be beneficial in oxidative stress-mediated inflammatory disorders.