• Molecules and Cells
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• 제27권2호
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• pp.251-255
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• 2009

Sepsis is the leading cause of death in critically ill patients. Today, around 60% of all cases of sepsis are caused by Gram-negative bacteria. The cell wall component lipopolysaccharide (LPS) is the main initiator of the cascade of cellular reactions in Gram-negative infections. The core receptors for LPS are toll-like receptor 4 (TLR4), MD-2 and CD14. Attempts have been made to antagonize the toxic effect of endotoxin using monoclonal antibodies against CD14 and synthetic lipopolysaccharides but there is as yet no effective treatment for septic syndrome. Here, we describe an inhibitory effect of a phosphatidylethanolamine derivative, PE-DTPA (phosphatidylethanolamine diethylenetriaminepentaacetate) on LPS recognition. PE-DTPA bound strongly to CD14 ($K_d$, $9.52{\times}10^{-8}M$). It dose dependently inhibited LPS-mediated activation of human myeloid cells, mouse macrophage cells and human whole blood as measured by the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and nitric oxide, whereas other phospho-lipids including phosphatidylserine and phosphatidylethanolamine had little effect. PE-DTPA also inhibited transcription dependent on $NF-{\kappa}B$ activation when it was added together with LPS, and it rescued LPS-primed mice from septic death. These results suggest that PE-DTPA is a potent antagonist of LPS, and that it acts by competing for binding to CD14.

• Journal of Periodontal and Implant Science
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• 제50권3호
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• pp.159-170
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• 2020

Purpose: Immunization with Porphyromonas gingivalis heat shock protein 60 (PgHSP60) may have an immunoregulatory effect on atherogenesis. The aim of this study was to determine whether nasal immunization with a PgHSP60 peptide could reduce atherosclerotic plaque formation in apolipoprotein E knockout (ApoE KO) mice. Methods: Seven-week-old male ApoE KO mice were assigned to receive a normal diet, a Western diet, a Western diet and challenge with PgHSP60-derived peptide 14 (Pep14) or peptide 19 (Pep19), or a Western diet and immunization with Pep14 or Pep19 before challenge with Pep14 or Pep19. Results: Atherosclerotic plaques were significantly smaller in mice that received a Western diet with Pep14 nasal immunization than in mice that received a Western diet and no Pep14 immunization with or without Pep14 challenge. An immunoblot profile failed to detect serum reactivity to Pep14 in any of the study groups. Stimulation by either Pep14 or Pep19 strongly promoted the induction of CD4⁺CD25⁺ forkhead box P3 (FoxP3)⁺ human regulatory T cells (Tregs) in vitro. However, the expression of mouse splenic CD4⁺CD25⁺FoxP3⁺ Tregs was lower in the Pep14-immunized mice than in the Pep14-challenged or Pep19-immunized mice. Levels of serum interferon gamma (IFN-γ) and transforming growth factor beta were higher and levels of interleukin (IL) 10 were lower in the Pep14-immunized mice than in the other groups. Induction of CD25^- IL-17⁺ T helper 17 (Th17) cells was attenuated in the Pep14-immunized mice. Conclusions: Nasal immunization with Pep14 may be a mechanism for attenuating atherogenesis by promoting the secretion of IFN-γ and/or suppressing Th17-mediated immunity.

• 분석과학
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• 제14권2호
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• pp.123-130
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• 2001

Perfluorinated sulfonated polymer-ethylenediamine(Nafion-en)이 화학수식된 유리탄소전극을 사용하여 Cd(II) 이온의 정량에 대해 연구하였다. Cd(II) 이온의 착화제인 ethylenediamine(en)을 nafion에 고정시켜 유리탄소전극 표면에 수식하면 이 수식전극의 en은 Cd(II) 이온과 $[Cd(en)_2]^{2+}$의 착물을 형성한다. Nafion-en이 화학수식된 유리탄소전극에서 시차펄스전압전류법에 의한 Cd(II) 이온의 환원봉우리전위는 $-0.780({\pm}0.005)V$(vs. Ag/AgCl), 측정범위는 $5.0{\times}10^{-7}-2.0{\times}10^{-5}M$, 검출한계(3s)는 $2.20{\times}10^{-7}M$이었다. Nafion-en이 화학수식된 유리탄소전극의 검출한계가 수식되지 않은 유리탄소전극에 비해 약 14배 정도 향상되었다.

• 환경생물
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• 제18권2호
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• pp.263-268
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• 2000

$Cd^{2+}$이 닭의장풀의 분리표피와 온전한 잎의 기공개폐에 미치는 영향을 조사하였다. $Cd^{2+}$을 분리표피에 처리하였을 때 기공열림이 촉진되었다. 100$\mu$M$Cd^{2+}$처리시 기공은 8.38$\mu\textrm{m}$까지 열렸으나, 대조구는 3.74$\mu\textrm{m}$였다. 대조구의 기공 크기는 일반적으로 작게 열렸다. 따라서, 분리표피가 생리적으로 건강한지를 조사하기 위해, 살리실릭산(SA)과 앱시스산(ABA)을 분리표피에 처리하여 기공크기를 측정하였다. 100$\mu$M SA와 1$\mu$M ABA는 기공열림을 각각 14%와 28% 억제하였다. 비슷한 효과가 다른 중금속인 $Al^{3+}과 Ag^{2+}$에서도 발견되는지 이들에 대한 기공개폐 효과를 살펴보았다. $Al^{3+}과 Ag^{2+}$도 기공열림을 각각 19%, 41%촉진하였다. 카드뮴에 의한 기공열림 기작을 이해하기 위해 K+흡수에 대한 카드뮴의 효과를 조사하였다. $Cd^{2+}$, SA 그리고 ABA는 분리표피에서 K+흡수를 각각 98%, 28%, 34% 억제하였다. $Cd^{2+}$이 온전한 잎에 미치는 기공개폐의 영향을 조사하기 위해 3주간 성장한 닭의장풀을 Hoagland용액(0.5mM $Cd^{2+}$, 10mM $Cd^{2+}$)에서 수경 배양한 후 온전한 잎의 기공전도도를 측정하였다. 그 결과, 기공전도도는 대조구에 비해 5mM $Cd^{2+}$과 10mM Cd$^{2+}$에서 각각 51%, 70%감소되었다. 따라서, $Cd^{2+}$은 닭의장풀의 분리표피와 온전한 잎의 기공개폐에 상반된 반응을 보이며, 분리한 표피에서 $Cd^{2+}$에 의한 기공열림은 $Cd^{2+}이 K^+$ 흡수를 방해하고, 자신이 공변세포로 들어가 팽압을 유도한 결과로 사료된다.

• 대한예방한의학회지
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• 제5권2호
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• pp.93-105
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• 2001

BACKGROUND : Changiga is a hetnal medicine which has been used of the traditional therapeutic agent of asthma. So I examine the effect of Changija on immune Cell&serum OA-specific IgE in BALF in rat asthma model. MATERIAL and METHODS : Rats were sensitized with OA; at day 1 sensitized group and Changiga(CIG) groups were systemically immunized by subcutaneous ingection of 1mg OA and 300mg of Al(OH)3 in a total volume of 2ml. At the same time, 1ml of 0.9% saline containing $6{\times}109$ B. pertussis bacilli was injected by i.p. 14 days, after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerocol containing 2%(wt/vol) OA, A day after local immunization, BAL fluid was collected from the rats. A day after local immunization, rats were orally administered with Changiga extract 14 days, Lymphocyte, CD4+ T-cell CD8+ T-cell counts, CD4+/CD8+ ratio in BALF, change of serum OA-specific IgE level in the peripheral blood were measured and evaluated. RESULT : Changiga showed a suppressive effect on a rat asthme model. Changiga decreased lymphocyte, CD4+ T-cell, CD4+/CD8+ ratio in BALF, serum OA-specific IgE level as compared with the control group, whereas Changiga decreased CD8+ T-cell in BALF with statistical nonsignificance as compared with the control group. CONCLUSION: This study shows that Changiga have a suppressive effect on rat allergic athma model. Changiga would be useful allergic asthma treatment agent.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.309-314
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• 2013

Aim: Brain tumors almost universally have fatal outcomes; new therapeutics are desperately needed and will only come from improved understandins of glioma biology. Methods: Exosomes are endosomally derived 30~100 nm membranous vesicles released from many cell types. Examples from GL26 cells were here purified using density gradient ultracentrifugation and monitored for effects on GL26 tumor growth in C57BL/6j mice (H-2b). Lactate dehydrogenase release assays were used to detect the cytotoxic activity of CD8+T and NK cells. Percentages of immune cells producing intracellular cytokines were analyzed by FACS. Results: In this study, exosomes from murine-derived GL26 cells significantly promoted in vivo tumor growth in GL26-bearing B6 mice. Then we further analyzed the effects of the GL26 cells-derived exosomes on immune cells including CD8+T, CD4+T and NK cells. Inhibition of CD8+T cell cytotoxic activity was demonstrated by CD8+T cell depletion assays in vivo and LDH release assays in vitro. The treatment of mice with exosomes also led to a reduction in the percentages of CD8+T cells in splenocytes as determined by FACS analysis. Key features of CD8+T cell activity were inhibited, including release of IFN-gamma and granzyme B. There were no effects of exosomes on CD4+T cells and NK cells. Conclusion: Based on our data, for the first time we demonstrated that exosomes from murine derived GL26 cells promote the tumor growth by inhibition of CD8+T cells in vivo and thus may be a potential therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6549-6556
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• 2013

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression and relapse, and thus represent a critical target for therapeutic intervention. Hence, it is extremely urgent to explore new therapeutic strategies directly targeting LSCs for acute myelogenous leukemia (AML) therapy. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), effectively inhibited human AML $CD34^+CD38^-$ cell proliferation in vitro culture in a dose-dependent manner while sparing normal hematopoietic stem and progenitor cells at physiologically achievable concentrations. Furthermore, ASP exerted cytotoxic effects on AML K562 cells, especially LSC-enriched $CD34^+CD38^-$ cells. Colony formation assays further showed that ASP significantly suppressed the formation of colonies derived from AML $CD34^+CD38^-$ cells but not those from normal $CD34^+CD38^-$ cells. Examination of the underlying mechanisms revealed that ASP induced $CD34^+CD38^-$ cell senescence, which was strongly associated with a series of characteristic events, including up-regulation of p53, p16, p21, and Rb genes and changes of related cell cycle regulation proteins P16, P21, cyclin E and CDK4, telomere end attrition as well as repression of telomerase activity. On the basis of these findings, we propose that ASP represents a potentially important agent for leukemia stem cell-targeted therapy.

• The Korean Journal of Physiology and Pharmacology
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• 제3권5호
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• pp.513-519
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• 1999

Direct exposure of renal tubular brush-border membranes (BBM) to free cadmium (Cd) causes a reduction in phosphate (Pi) transport capacity. Biochemical mechanism of this reduction was investigated in the present study. Renal proximal tubular brush-border membrane vesicles (BBMV) were isolated from rabbit kidney outer cortex by Mg precipitation method. Vesicles were exposed to $50{\sim}200\;{\mu}M\;CdCl_2$ for 30 min, then the phosphate transporter activity was determined. The range of Cd concentration employed in this study was comparable to that of the unbound Cd documented in renal cortical tissues of Cd-exposed animals at the time of onset of renal dysfunction. The rate of sodium-dependent phosphate transport $(Na^+-Pi\;cotransport)$ by BBMV was determined by $^{32}P-Iabeled$ inorganic phosphate uptake, and the number of $Na^+-Pi$ cotransporters in the BBM was assessed by Pi-protectable $^{14}C-labeled$ phosphonoformic acid $([^{14}C]PFA)$ binding. The exposure of BBMV to Cd decreased the $Na^+-Pi$ cotransport activity in proportion to the Cd concentration in the preincubation medium, but it showed no apparent effect on the Pi-protectable PFA binding. These results indicate that an interaction of renal BBM with free Cd induces a reduction in $Na^+-Pi$ cotransport activity without altering the carrier density in the membrane. This, in turn, suggest that the suppression of phosphate transport capacity $(V_{max})$ observed in Cd-treated renal BBM is due to a reduction in $Na^+-Pi$ translocation by existing carriers, possibly by Cd-induced fall in membrane fluidity.

• Toxicological Research
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• 제26권2호
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• pp.131-136
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• 2010

The time-dependent changes in cadmium (Cd) concentration were studied in Female Sprague-Dawley (SD) rats during and after Cd exposure via drinking water (10 and 50 ppm) for 30 days. The cadmium concentration in muscle, liver, kidney, blood plasma, and urine, and the metallothionein concentration in blood plasma were determined every 10 days during exposure and every 7 days after exposure for 3 weeks. The muscle Cd concentration did not change during, and neither after, exposure. The liver Cd concentration increased from 1.4 to 3.3 (at 10 ppm) and from 6.1 to 10.1 folds (at 50 ppm) during exposure and remained higher than those of controls in both groups even during post-exposure period. The kidney Cd concentrations were 2.3 to 5.1 (at 10 ppm) and 4.9-14.0 folds (at 50 ppm) higher than those of controls during exposure and also remained elevated during the post-exposure period. Plasma Cd concentrations were not significantly different from those of controls in both groups. Urine Cd concentrations were more than 2 folds (at 10 ppm) and 6.5 to 12.6 folds (at 50 ppm) higher than those of controls but rapidly decreased over the 7 days of withdrawal. Blood plasma metallothionein concentrations were more than 2.4 folds (at 10 ppm) and 3.1 to 7.4 folds (at 50 ppm), and they remained elevated till 7 days (10 ppm) and 14 days (at 50 ppm) after exposure. Our data support that Cd in urine could be a useful biomarker during Cd exposure period and metallothionein in blood plasma could be as a supportive biological marker for during and post Cd exposure.

• 한국토양비료학회지
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• 제18권1호
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• pp.99-104
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• 1985

Cd이 오염(汚染)된 농경지(農耕地) 토양(土壤)에서 수도(水稻)를 재배(栽培)할 때에 수도(水稻)의 생육(生育), 수량(收量) 및 Cd흡수(吸收)에 미치는 토양중(土壤中) 유기물(有機物)과의 관계(關係)를 알기 위하여, 유기물(有機物)로 원예용(園藝用) 부엽토(腐葉土)를 첨가(添加)하고 Cd염(鹽)을 토양처리(土壤處理)하여 수도(水稻)를 Pot재배(栽培)한 결과(結果)를 요약(要約)하면 다음과 같다. (1) 토양중(土壤中) 유기물(有機物)의 증가(增加)로 Cd에 의한 수도(水稻)의 생육피해(生育被害)를 줄일 수 있었다. (2) 토양중(土壤中) 유기물(有機物)의 증가(增加)는 수도체(水稻體)의 지상부위(地上部位) 즉(卽), 엽초, 간(稈), 엽신(葉身) 및 현미중(玄米中)의 Cd 함량(含量)을 감소(減少)시킬 수 있었다. (3) 수도체(水稻體) 지상부위(地上部位)의 Cd 함유량(含有量)은 엽초, 간(稈), 엽신(葉身), 현미(玄米) 순(順)으로 낮았다. (4) 수도(水稻)의 계속(繼續) 담수재배(湛水栽培)는 Cd 25ppm 처리(處理)에서도 현미중(玄米中) Cd 함량(含量)이 오염미(汚染米) 판정기준치(判定基準値) 1ppm 이하(以下)인 0.59ppm이었다. (5) 담수상태하(湛水狀態下)에서 부엽토(腐葉土) 200g/건토(乾土) 8kg과 Cd 농도(濃度) 25ppm 처리(處理)로 현미중(玄米中) Cd 함량(含量)을 우리나라 비오염지(非汚染地) 답토양(畓土壤)에서 생산(生産)되는 현미중(玄米中) Cd 함량(含量)과 거의 유사(類似)한 0.14ppm으로 억제(抑制)되었다.