• Title/Summary/Keyword: $CD4^+$

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Cryptotanshinone Induces Inhibition of Breast Tumor Growth by Cytotoxic CD4+ T Cells through the JAK2/STAT4/ Perforin Pathway

  • Zhou, Jun;Xu, Xiao-Zhen;Hu, Yao-Ren;Hu, Ai-Rong;Zhu, Cheng-Liang;Gao, Guo-Sheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2439-2445
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    • 2014
  • Cryptotanshinone (CPT), is a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miotiorrhiza bunge. Numerous researchers have found that it could work as a potent antitumor agent to inhibit tumor growth in vitro, buith there has been much less emphasis on its in vivo role against breast tumors. Using a mouse tumor model of MCF7 cells, we showed that CPT strongly inhibited MCF7 cell growth in vivo with polarization of immune reactions toward Th1-type responses, stimulation of naive CD4+ T cell proliferation, and also increased IFN-${\gamma}$ and perforin production of CD4+ T cells in response to tumor-activated splenocytes. Furthermore, data revealed that the cytotoxic activity of CD4+ T cells induced by CPT was markedly abrogated by concanamycin A(CMA), a perforin inhibitor, but not IFN-${\gamma}$ Ab. On the other hand, after depletion of CD4+ T cells or blocked perforin with CMA in a tumor-bearing model, CPT could not effectively suppress tumor growth, but this phenomenon could be reversed by injecting naive CD4+ T cells. Thus, our results suggested that CPT mainly inhibited breast tumor growth through inducing cytotoxic CD4+ T cells to secrete perforin. We further found that CPT enhanced perforin production of CD4+ T cells by up-regulating JAK2 and STAT4 phosphorylation. These findings suggest a novel potential therapeutic role for CPT in tumor therapy, and demonstrate that CPT performs its antitumor functions through cytotoxic CD4+ T cells.

The Effects of Gamichunggumgangwha-tang (Jiaweiqingjinjianghuo-tang) and Gamiyukmigiwhang-tang (Jiaweiliuweidihuang-tang) on Immune Cell & Serum OA-specific IgE in BALF in a Rat Asthma Model (가미청금항화탕 및 가미육미지황탕이 Allergy 천식 모델 흰쥐의 BALF내 면역세포 및 혈청 IgE에 미치는 영향)

  • 조영민;정희재;정승기;이형구
    • The Journal of Korean Medicine
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    • v.24 no.3
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    • pp.1-10
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    • 2003
  • Background : Asthma is a chronic inflammatory disorder under immunological influence. Gamichunggumgangwha-tang (CG, Jiaweiqingjinjianghuo-tang) and Gamiyukmigiwhang-tang (YM, Jiaweiliuweidihuang-tang) are herbal tonics for asthma from traditional herbal medicine. Objective : To evaluate the effect of CG and YM on immune cell & serum OA-specific IgE in broncho-alveolar lavage fluid (BALF) in a rat asthma model. Materials and Methods : Rats were sensitized with OA; at day I sensitized group and CG and YM groups were systemically immunized by subcutaneous injection of 1mg OA and 300mg of Al(OH)3 in a total volume of 2ml. At the same time, 1 ml of 0.9% saline containing $6{\times}10^9$ B. pertussis bacilli was injected by Lp. 14 days after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerosol containing 2% (wt/vol) OA. A day after local immunization, BALF was collected from the rats. Rats were orally administered with each of CG and YM extract for 14 days since the day after local immunization. Lymphocyte, CD4+ T cell and CD8+ T cell counts, CD4+/CD8+ ratio in BALF, change of serum OA-specific IgE level, CD4+ T cell and CD8+ T cell percentages in the peripheral blood were measured and evaluated. Results : CG and YM showed an alleviating effect on asthmatic responses of rats. CG decreased total cell, lymphocyte, CD4+ T cells in BALF, and serum OA-specific IgE level as compared with the control group. YM decreased lymphocytes as compared with the control group. CD4+/CD8+ ratio in BALF from the CG and YM groups and serum OA-specific IgE level from the YM group didn't show any significant variation from the control group. Conclusion : CG alleviated asthmatic hyperreactivity of the immune system through CD4+ T cells and serum IgE. Further the study of this immune system modulating mechanism is expected.

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Peripheral Generation of $CD4^+CD25^+Foxp3^+$ Regulatory T Cells

  • Kim, Byung-Seok;Park, Young-Jun;Kang, Chang-Yuil
    • IMMUNE NETWORK
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    • v.7 no.1
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    • pp.1-9
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    • 2007
  • [ $CD4^+CD25^+$ ] regulatory T cells (Tregs) expressing the lineage-specific marker Foxp3 represent an important regulatory T cell that is essential for maintaining peripheral tolerance. Although it was believed that Treg development is solely dependent on the thymus, accumulating evidence demonstrates that Tregs can also be induced in the periphery. Considering the various origins of peripherally developed $CD4^+CD25^+Foxp3^+$ regulatory T cells, it seems likely that multiple factors are involved in the peripheral generation of Tregs.

Dynamic lipopolysaccharide transfer cascade to TLR4/MD2 complex via LBP and CD14

  • Kim, Soo Jin;Kim, Ho Min
    • BMB Reports
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    • v.50 no.2
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    • pp.55-57
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    • 2017
  • Toll-like receptor 4 (TLR4) together with MD2, one of the key pattern recognition receptors for a pathogen-associated molecular pattern, activates innate immunity by recognizing lipopolysaccharide (LPS) of Gram-negative bacteria. Although LBP and CD14 catalyze LPS transfer to the TLR4/MD2 complex, the detail mechanisms underlying this dynamic LPS transfer remain elusive. Using negative-stain electron microscopy, we visualized the dynamic intermediate complexes during LPS transfer-LBP/LPS micelles and ternary CD14/LBP/LPS micelle complexes. We also reconstituted the entire cascade of LPS transfer to TLR4/MD2 in a total internal reflection fluorescence (TIRF) microscope for a single molecule fluorescence analysis. These analyses reveal longitudinal LBP binding to the surface of LPS micelles and multi-round binding/unbinding of CD14 to single LBP/LPS micelles via key charged residues on LBP and CD14. Finally, we reveal that a single LPS molecule bound to CD14 is transferred to TLR4/MD2 in a TLR4-dependent manner. These discoveries, which clarify the molecular mechanism of dynamic LPS transfer to TLR4/MD2 via LBP and CD14, provide novel insights into the initiation of innate immune responses.

Effect of Sipjundaebotang on the immune response of CD4+ and CD8+ T cell in rats (십전대보탕(十全大補湯)이 CD4+ 및 CD8+ T세포수(細胞數)에 미치는 영향(影響))

  • Ko, Young-Kwon;Ryu, Bong-Ha;Park, Dong-Won;Ryu, Ki-Won
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.4 no.1
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    • pp.111-129
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    • 1998
  • In order to research the effect of Sipjundaebotang on the immune respons of CD4+ T cell and CD8+ T cell in rats, author have performed this experimental study. Experimental groups are divided into 5 groups(intact, control, sample I, sample II, sample III). Normal group was intact, control group was administrated normal saline 2cc for 5 days, sample I was administrated low concentration of Sipjundaebotang(100/3100pack/ml) 2cc for 5 days, sample II was administrated middle concentration of Sipjundaebotang(500/3100pack/ml) 2cc for 5 days, sample III was administrated high concentration of Sipjundaebotang(2500/3100pack/ml) 2cc for 5 days. WBC, Lymphocyte, CD4+ T cell in the blood, spleen, axillary node and CD8+ T cell in the blood, spleen and axillary node were determined. The results was as follows: 1. WBC count in blood was significantly decrcased in the control, sample I, II, III groups as compared with the normal group. 2. Lymhocyte count in the blood was significantly decreased in the control, sample I, II groups as compared with the normal group. 3. CD4+ T cell count in the blood was significantly increased dose-dependently in the sample I, II, III groups as compared with the normal group. 4. CD4+ T cell count in the spleen was significantly increased in the sample I, II, III groups as compared with the normal group. 5. CD4+ T cell count in the axillary node was significantly increased in the sample III group as compared with the normal group, however significantly decreased in the sample I, II groups as compared with the normal group. 6. CD8+ T cell count in the blood was significantly increased in the sample III groups as compared with the normal group. 7. CD8+ T cell count in the spleen was significantly increased in the sample I, II, III groups as compared with the normal group. but there was no differences in the sample groups. 8. CD8+ T cell count in the axillary node was decreased in the sample I, II groups as compared with the normal group.

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The Effect of Thermal Annealing and Growth of CdGa2Se4 Single Crystal Thin Film by Hot Wall Epitaxy (Hot Wall Epitaxy(HWE)법에 의한 CdGa2Se4 단결정 박막 성장과 열처리 효과)

  • Hong, Myung-Seok;Hong, Kwang-Joon
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.20 no.10
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    • pp.829-838
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    • 2007
  • The stochiometric mix of evaporating materials for the $CdGa_2Se_4$ single crystal thin films was prepared from horizontal furnace. To obtain the single crystal thin films, $CdGa_2Se_4$ mixed crystal was deposited on thoroughly etched semi-insulating GaAs(100) substrate by the Hot Wall Epitaxy (HWE) system. The source and substrate temperature were $630^{\circ}C$ and $420^{\circ}C$, respectively. The crystalline structure of single crystal thin films was investigated by the photoluminescence and double crystal X-ray diffraction (DCXD).The carrier density and mobility of $CdGa_2Se_4$ single crystal thin films measured from Hall effect by van der Pauw method are $8.27{\times}10^{17}\;cm^{-3},\;345\;cm^2/V{\cdot}s$ at 293 K. respectively. The temperature dependence of the energy band gap of the $CdGa_2Se_4$ obtained from the absorption spectra was well described by the Varshni's relation, $Eg(T)\;=\;2.6400\;eV\;-\;(7.721{\times}10^{-4}\;eV/K)T^2/(T+399\;K)$. After the as-grown single crystal $CdGa_2Se_4$ thin films were annealed in Cd-, Se-, and Ga -atmospheres, the origin of point defects of single crystal $CdGa_2Se_4$ thin films has been investigated by PL at 10 K. The native defects of $V_{Cd}$, $V_{Se}$, $Cd_{int}$, and $Se_{int}$ obtained by PL measurements were classified as donors or accepters. We concluded that the heat-treatment in the Cd-atmosphere converted single crystal $CdGa_2Se_4$ thin films to an optical p-type. Also, we confirmed that Ga in $CdGa_2Se_4/GaAs$ did not form the native defects because Ga in single crystal $CdGa_2Se_4$ thin films existed in the form of stable bonds.

The effects of zeatin on Cd2+ -induced physiological toxicities in Commelina communis L (Zeatin이 Cd2+에 의한 닭의장풀의 생리적 독성에 미치는 영향)

  • Lee Joon Sang
    • Journal of Environmental Science International
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    • v.14 no.3
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    • pp.345-350
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    • 2005
  • Three-week old Commelina communis was transferred and grown in Hoagland solution containing $100{\mu}M\;Cd^{2+},\;100{\mu}M\;Cd^{2+}+100{\mu}M\;kinetin,\;100{\mu}M\;Cd^{2+}+100{\mu}M\;zeatin\;and\;100{\mu}M\;Cd^{2+},\;200{\mu}M$ zeatin for 7 days, and then a number of physiological activities were investigated. In control, the length of the stem of plants was increased to 4.7cm, but in $Cd^{2+},\;Cd^{2+}+kinetin,\; Cd^{2+}+100{\mu}M\;zeatin\;and\;Cd^{2+}+200{\mu}M$ zeatin treatments, the growth of plants were increased to 1.5cm, 2.1cm, 3.9cm and 4.3 em, respectively. In the treatments of $Cd^{2+},\;Cd^{2+}+kinetin,\;Cd^{2+}+100{\mu}M\;zeatin\;and\; Cd^{2+}+200{\mu}M$ zeatin, total chlorophyll contents were reduced to $26\%,\;24\%,\;15\%\;and\;3\%$, respectively, on the contrast to the control. In chlorophyll fluorescence experiments, Fv/Fm ratios were also reduced to $44\%,\;21\%,\;17\%\;and\;5\%$ in the light intensity of $2100{\mu}Mmole\;E\;m^{-2}s^{-1}\;by\;Cd^{2+},\;Cd^{2+}+kinetin,\;Cd^{2+}+$100{\mu}M\;zeatin\;and\;Cd^{2+}+200{\mu}M$ zeatin treatments on the contrast to the control. Water stresses were increased to 2.6, 1.7 and 1.2 times by $Cd^{2+},\; Cd^{2+}+kinetin\;and\;Cd^{2+}+{\mu}M$ zeatin. On the other hand, combination of $Cd^{2+}+200{\mu}M$ zeatin reduced water stress to $0.12\%$. In $Cd^{2+}$ accumulation experiments $Cd^{2+}$transports were inhibited to $33\%\; 48\%\;and\;70\%\;by\;Cd^{2+}+kinetin,\;Cd^{2+}+100{\mu}M\;zeatin\;and\;Cd^{2+}+200{\mu}M$ zeatin. Therefore, it could be concluded that zeatin clearly reduced the toxicities of $Cd^{2+}$ by reducing the absorption of $Cd^{2+}$.

Suppressive effects of Sojinjiyangtang(SJJY) on Der f-induced Atopic Dermatitis in NC/Nga Mice. (NC/Nga 생쥐에 유발된 아토피 피부염에 대한 소진지양탕(消疹止痒湯)의 억제 효과와 면역 조절 작용)

  • Lee, Won-Gu;Jin, Mi-Rim;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.16 no.2
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    • pp.171-190
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    • 2007
  • Atopic dermatitis is a chronic inflammatory skin disease characterized by pruritic and erythromatous skin lesions. In this study we examined the suppressive effects of SJJY on der f induced atopic dermatitis in NC/Nga mic, and concluded as follows: Oral administration of SJJY significantly decreased the severity score in the skin lesions at the dosage of 6.6 mg/25g/day for 8 weeks. SJJY significantly suppressed the infiltration of inflammatory cells into skin compared with control, and decreased the expression of CD4, CD8, CD20 and CCR3 in the skin lesions. SJJY significantly decreased the level of IgE in the serum compared with control, and the levels of IgM, IgG2a and IgG2b were also decreased. SJJY significantly decreased the levels of IL-6, but not TNF-a, in the serum compared with control. The levels of IFN-$\gamma$ was significantly increased in the supernatant of CD3/CD28 activated cultured splenocytes from the SJJY treated mice. The levels of IL-4 and IFN-$\gamma$ in the supernatants was much less in the der f activated splenocytes from SJJY treated mice than control. SJJY significantly increased the total number of cells in lymph node, while decreased the total number of skin compared with control. SJJY increased the number of CD3+ and CD4+ cell compared with control, while decreased the number of CD4+/CD25+ and CCR3+ cells in the PBMC. SJJY increased the number of CD3+, CD4+, CD8+, CD4+/CD25+, NKT+, CD3+/CD69+ cells compared with control, while decreased the number of B220+/IgE+, B220+/CD23+ cells in the lymph node. SJJY significantly decreased the number of CD3+/CD69+, CCR3+, B220+/IgE+, CD11b+/Gr-1+ compared with control in the skin lesions. Taken together, these results suggested that SJJY has suppressive effects on atopic dermatitis by the regulation of immune system and has potential as a therapeutics for atopic dermatitis. Further studies on molecular mechanisms on immune regulation are needed.

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113Cd and 133Cs NMR Study of Nucleus-Phonon Interactions in Linear-Chain Perovskite-Type CsCdBr3

  • Park, Sung Soo;Lim, Ae Ran
    • Journal of the Korean Magnetic Resonance Society
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    • v.20 no.4
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    • pp.109-113
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    • 2016
  • Resonance frequencies from the $^{113}Cd$ and $^{133}Cs$ nuclear magnetic resonance (NMR) spectra for the $CsCdBr_3$ single crystal were measured at varying temperatures by the static NMR method. The temperature-dependent changes of these frequencies are related to the changing structural geometry of the ${CdBr_6}^{4-}$ units, which affects the environment of $^{133}Cs$. The spin-lattice relaxation rates ($1/T_1$) for the $^{113}Cd$ and $^{133}Cs$ nuclei were measured in order to obtain detailed information about the dynamics of $CsCdBr_3$ crystals. The dominant relaxation mechanisms for $^{113}Cd$ and $^{133}Cs$ nuclei are direct single-phonon and Raman spin-phonon processes, respectively.

The Effect of Dietary Low Iron Levels on the Metabolism of Iron in Long Termm Cadmium Poisoned Rats (장기간의 철분 부족 식이가 카드뮴중독된 흰쥐의 철분대사에 미치는 영향)

  • 최미경;김애정;승정자
    • Journal of the East Asian Society of Dietary Life
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    • v.4 no.2
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    • pp.9-16
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    • 1994
  • This study was undertaken to investigate the effects of dietary low (Fe) levels on Fe metabolism of cadmium(Cd) poisoned rats. 40 male Sprague weaning Dawley rats weighing 80-90g were divided into 4 groups(LFe:low Fe, LFeCd:low Fe and Cd, AFe: adequate Fe, AFeCd: adequate Fe and Cd) according to Cd administration(0, 50ppm in drinking water) and Fe levels(Fe:6ppm, 40ppm in diet)for 12 weeks. The food intake and body weight gain of Cd group with low Fe(LFeCd) were significantly lower than those of without Cd group with adequate Fe(AFe)(p<0.01, P<0.05). But there was no significantly difference between Cd groups and without Cd groups in water intake. The blood levels of hemoglobin, hematocrit, and serum levels of Fe of LFeCd were significantly lower than those of AFe(p<0.01, p<0.05, p<0.001). The urinary and fecal excretion of Fe of LFeCd was significantly lower than that of AFe(p<0.05, p0.05). The levels of Fe of liver, spleen in LFeCd were lower than those of AFeCd(p<0.05, p<0.05). These results indicates that adequate iron supplementation to Cd pretreated rats induce protective effects on the reduction of Fe status by Cd poisoning.