• Clinical and Experimental Pediatrics
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• 제51권7호
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• pp.754-759
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• 2008

목 적 : 알레르기 질환의 증가가 Th1/Th2 세포 면역의 불균형에 의한다는 것은 널리 받아들여지고 있다. 이에 본 연구에서는 미숙아의 제대혈에서 Th2 세포의 다른 사이토카인 분비를 증가시키는 IL-4, Th1 세포 분화를 억제하는 IL-10 및 강한 Th2 세포 억제 작용을 하는 IL-12를 측정하여 그 상관관계를 알아보고자 하였다. 방 법 : 2003년 1월부터 2005년 7월까지 이화여자대학교 부속 목동병원에서 출생한 34주 미만의 미숙아 중 보호자 동의하에 제대혈 검사가 가능하였던 46명을 대상으로 하여 의무기록을 통해 대상아의 천명의 발현 여부, 천식의 발생 여부에 대한 자료를 얻었다. 제대혈은 출생 시 채취하여, 즉시 혈청을 원심 분리하여 $-70^{\circ}C$ 냉동고에 보관하였다가 ELISA법을 이용하여 IL-4, IL-10 및 IL-12를 측정하였다. 결 과 : 관찰 기간은 12개월에서 36개월로 평균 16.0개월${\pm}13.2$일 이었고, 연구 기간 중 천명군은 18명이었으며, 비천명군과 비교하였을 때 IL-12가 유의하게 낮았다($366.60{\pm}140.40pg/mL$ vs. $435.10{\pm}91.20pg/mL$, P=0.009). IL-10은 천명군이 비천명군에 비해 높은 수치를 보였으나($2.60{\pm}5.11pg/mL$ vs $0.40{\pm}0.39pg/mL$) 통계적 의의는 없었다. IL-4는 차이가 없었다. 천식군은 4명으로 이들의 IL-12은 $282.60{\pm}128.88pg/mL$, 비천식 천명군 $392.40{\pm}138.06pg/mL$, 비천명군 $435.10{\pm}91.20pg/mL$로 세 군 사이에 유의한 차이가 있었다(P=0.045). 결 론 : 천명 및 천식이 발생한 영아에서 제대혈 IL-12 수치가 낮아 출생 시부터 면역학적인 불균형이 있었음을 예상할 수 있으며, 제대혈의 IL-12 수치로 생후 알레르기 호흡기 질환 발생을 예측하여 출생 시부터 보다 적극적인 알레르기 질환의 예방에 기여할 수 있을 것으로 생각된다.

• 대한약침학회지
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• 제13권3호
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• pp.63-71
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• 2010

Objectives: Gallic acid (GA) is the major component of tannin which could be easily founded in various natural materials such as green tea, red tea, grape juice, and Corni Fructus. The purpose of this study is to investigate the effect of Gallic acid (GA) on production of interleukin (IL) in mouse macrophage Raw 264.7 cells stimulated by lipopolysaccharide (LPS). Methods: Productions of interleukins were measured by High-throughput Multiplex Bead based Assay with Bio-plex Suspension Array System based on $xMAP^{(R)}$ (multi-analyte profiling beads) technology. Firstly, cell culture supernatant was obtained after treatment with LPS and GA for 24 hour. Then, it was incubated with the antibody-conjugated beads for 30 minutes. And detection antibody was added and incubated for 30 minutes. And Strepavidin-conjugated Phycoerythrin (SAPE) was added. After incubation for 30 minutes, the level of SAPE fluorescence was analyzed on Bio-plex Suspension Array System and concentration of interleukin was determined. Results: The results of the experiment are as follows. 1. GA significantly inhibited the production of IL-3, IL-10, IL-12p40, and IL-17 in LPS-induced mouse macrophage RAW 264.7 cells at the concentration of 25, 50, 100, 200 uM (p<0.05). 2. GA significantly inhibited the production of IL-6 in LPS-induced mouse macrophage RAW 264.7 cells at the concentration of 50, 100, 200 uM (p<0.05). 3. GA diminished the production of some cytokine such as IL-4, IL-5, and IL-13 in LPS-induced mouse macrophage RAW 264.7 cells. 4. GA did not show the inhibitory effect on the production of IL-$1{\alpha}$ and IL-9 in LPS-induced mouse macrophage RAW 264.7 cells. Conclusions: These results suggest that GA has anti-inflammatory activity related with its inhibitory effects on the production of interleukins such as IL-3, IL-10, IL-12p40, IL-17, and IL-6 in LPS-induced macrophages.

• The Korean Journal of Physiology and Pharmacology
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• 제27권5호
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• pp.471-479
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• 2023

Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs' survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.

• 대한한방종양학회지
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• 제8권1호
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• pp.93-101
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• 2002

Objectives This experimental study was carried out to evaluate the effects of Phellinus Linteus on immune activation. Methods In order to investigate the effect of Phellinus Linteus, the following was performed: The fraction of $CD4^+$, $CD8^+$, $CD19^+$ in splenic cell, gene expression of IL-12 (p35), IL-12 (p40) , $IFN-{\gamma}$, and splenic cell proliferation by PL-E. Results PL-E helped $CD4^+$, $CD8^+$, $CD19^+$ expression more effectively compared with control group. PL-E helped IL-12 (p35), IL-12 (p40), $IFN-{\gamma}$ gene expression in splenic cells more effectively compared with control group. PL-E proliferated splenic cells more effectively compared with control group. Conclusions: It is suggested that PL-E is able to activate immune response system.

• 대한수의학회지
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• 제44권2호
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• pp.163-169
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• 2004

To elucidate the molecular mechanisms of autoimmune inflammation in the central nervous system, we examined the expression and localization of STAT1, STAT3, STAT4 and STAT6 molecules during experimental autoimmune encephalomyelitis (EAE) by competitive PCR. In the present study, we quantitated IL-4 and IL-12 p40 mRNA by competitive PCR in the CNS during EAE. IL-4 mRNA was found at early and peak stages. On the other hand, the IL-12 p40 mRNA level reached maximal levels at the peak stage and still found at the recovery stage of the disease. We examined the kinetics of STAT mRNA in the CNS during EAE and demonstrated that STAT1 and STAT4 mRNA reached a maximal level at the peak stage of EAE, whereas STAT3 mRNA level increased gradually to the recovery stage. STAT6 mRNA increased rapidly at the early stage followed by gradual decrease till the recovery stage. Taken together, these findings suggest that STAT4 which was probably activated by IL-12 plays a pro-inflammatory role and that STAT3 which was activated throughout the disease course seems to serve as a transducer of anti-inflammatory signals.

• 혜화의학회지
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• 제10권2호
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• pp.179-188
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• 2002

This experimental study was carried out to evaluate the effects of Acanthopanacis cortex on Cytokine-inducing and and immune response in Mice. In order to investigate the effect of Acanthopanacis cortex, the following was performed; Cytotoxicity, in vitro, the fraction of $CD4^+$, $CD8^+$, $B220^+$ in splenic cell, gene expression of IL-12(p35), IL-12(p40), IFN-${\gamma}$, and splenic cell proliferation by Acanthopanacis cortex. Analysis of cytokine gene expression was carried out by RT-PCR amplification. Amplified PCR products were electrophoresed on 1.2% agarose gel, and the analysis (Ht) was used to 1D-density program. The results were obtained as follows. Acanthpanacis cortex showed didn't have cell toxicity under $12{\mu}g/m{\ell}$ group on mouse lung fibroblast cells. In an in vitro model using mouse peripheral blood mononuclear cells (PBMCs), extract of Acanthpanacis cortex induced multiple cytokine, including interleukin-12 (p35), interleukin-12 (p40), interferon-gamma (IFN-${\gamma}$). The extract also enhanced the percentages of the $CD4^+$, and $CD8^+$ in the untreated control were $22.1{\pm}3.3$ to $38.4{\pm}2.1$, and $5.0{\pm}0.4$ to $10.7{\pm}0.3%$, respectively. From above findings, it is suggested that Acanthopanacis cortex is able to anti-cancer and activate immune response system.

• 동의생리병리학회지
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• 제17권4호
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• pp.898-904
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• 2003

Pellinus linteus has been used for the prevention of cancer traditionally. There are three origins of Pellinus linteus, Korea, China and Cambodia. However, their immunological activities were not evlauated comparatively. Thus, this study was done to evaluate immunomodulatory effects of Phellinus linteus(PL) from Korea, china and cambodia, We confirmed PL showed two major protein bands, 50 kDa and 80 kDa by protein analysis. These PL effectively upregulated the expressions of IL-2 at 10 ug/ml and GM-CSF, IL-4, IL-10, IL-12(p35), IL-12(p40), IL-18, IFN-r in all concentrations. However, Korea-PL upregulated the expression of IL-12 more effectively than the other PLs. It intended to increase NO with no significance. Those results indicate Phellinus linteus had cytokine modulating effect

• Tuberculosis and Respiratory Diseases
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• 제45권2호
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• pp.301-310
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• 1998

연구배경: 결핵성 흉막염은 면학적으로 흉강내에 국소적으로 활성화된 CD4+ T림프구와 대식세포가 관여하는 세포매개면역이 중요한 역할을 하며 이들의 상호작용은 다양한 사이토카인에 의해 좌우된다고 알려져 있다. 특히 helper T cell type 1 (Th1) 사이토카인인 IL-12 및 IFN-$\gamma$와 Th2 사이토카인인 IL-4 및 IL-10간의 균형이 세포매개반응의 정도를 결정한다고 생각되고 있다. 본 연구는 세포매개면역반응의 지표로서 Th1 사이토카인인 IL-12, IFN-$\gamma$와 이들과 길항적으로 작용한다고 알려져있는 Th2 사이토카인 중 IL-10이 결핵성 흉수내에 어떻게 표현되는지를 검사하여 대조군인 악성 흉수와 비교함으로써 결핵성 흉막염의 변역학적 기전을 이해하는데 도움이 되고자 하였으며 아울러 사이토카인의 진단적 유용성을 알아보고자 하였다. 방 법: 각 20명의 결핵성 흉막염과 악성 흉막염 환자를 대상으로 흉수와 혈장에서 IL-10, IL-12, IFN-$\gamma$를 측정하고 흉수에서의 ADA를 측정하여 비교하였다. 사이토카인은 대상환자의 혈액과 흉수를 원심분리하여 얻은 상층액을 ELISA 방법으로 측정하였고 ADA 활성도는 비색법으로 측정하였다. 결 과: 결핵성 흉막염 환자에서 흉수의 IL-10, IL-12, IFN-$\gamma$의 농도는 $121.3{\pm}83.7$ pg/mL, $571.4{\pm}472.7$ pg/mL, $420.4{\pm}285.9$ pg/mL로 혈장의 $21.2{\pm}60.9$ pg/mL, $194.5{\pm}67.6$ pg/mL, $30.1{\pm}18.3$ pg/mL 보다 모두 유의하게 높았다 (p<0.01). 악성 흉막염 환자에서 흉수의 IL-10, IL-12, IFN-$\gamma$의 농도는 $88.4{\pm}40.4$ pg/mL, $306.5{\pm}271.1$ pg/mL, $30.5{\pm}54.8$ pg/mL로 혈장의 $43.4 {\pm}67.2$ pg/mL, $206.8{\pm}160.6$ pg/mL, $14.6{\pm}3.3$ pg/mL와 비교하였을때 IL-10 만이 유의하게 높았고 (p<0.001) IL12, IFN-$\gamma$에선 유의한 차이가 없었다. 결핵성 흉막염과 악성 흉막염 환자의 흉수에서의 농도를 비교하였을 때 IL-12, IFN-$\gamma$, ADA는 결핵성 흉막염에서 유의하게 높았으나 (p=0.046, <0.001, <0.001) IL-10은 유의한 차이가 없었다. 결핵성 흉수염을 악성 흉수염과 감별하는데 있어 IL-12, IFN-$\gamma$, ADA의 기준을 각각 300 pg/mL, 100 pg/mL, 45 U/L으로 하였을때 민감도/특이도는 IL-12에서 60%/70%, IFN-$\gamma$에서 90%/85%, ADA 에서 85%/90%였다. 결 론: 결핵성 흉수에서 흉강내에 Th1 사이토카인인 IL-12, IFN-$\gamma$와 함께 IL-10이 증가되어 있었고 악성흉수와 비교했을때 IL-12, IFN-$\gamma$는 유의하게 증가되어 있었으나 IL-10은 의의가 없었다. 따라서 결핵성 흉막염의 면역기전에 Th1 경로의 세포매개변역반응이 주로 관여함을 확인할 수 있었고 국소적인 IL-10 증가의 임상적 의의는 추후의 연구가 필요할 것으로 생각된다. 또한 IFN-$\gamma$와 ADA는 결핵성 흉수와 악성 흉수와의 감별에 유용한 진단법으로 생각된다.

• Parasites, Hosts and Diseases
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• 제61권2호
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• pp.138-146
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• 2023

Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses. Dendritic cells (DCs) are the most prominent type of antigen-presenting cells and regulate the host immune response, including the response of T-cells. However, differences in the DC responses of these mouse strains to T. gondii infection have yet to be characterized. In this study, we cultured bone marrow-derived DCs (BMDCs) from BALB/c and C57BL/6 mice. These cells were infected with T. gondii. The activation of the BMDCs was assessed based on the expression of cell surface markers and cytokines. In the BMDCs of both mouse strains, we detected significant increases in the expression of cell surface T-cell co-stimulatory molecules (major histocompatibility complex (MHC) II, CD40, CD80, and CD86) and cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12p40, IL-1β, and IL-10) from 3 h post-T. gondii infection. The expression of MHC II, CD40, CD80, CD86, IFN-γ, IL-12p40, and IL-1β was significantly higher in the T. gondii-infected BMDCs obtained from the C57BL/6 mice than in those from the BALB/c mice. These findings indicate that differences in the activation status of the BMDCs in the BALB/c and C57BL/6 mice may account for their differential susceptibility to T. gondii.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.435-441
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• 1998

We examined effects of interleukin $1{\alpha}$ ($IL1{\alpha}$) and phorbol 12, 13 dibutyrate (PDB), an activator of protein kinase C, on mRNA for Prostaglandin H synthase (PGHS) and prostanoid production in cultured ovine meningeal fibroblasts. Immuno- and morphologically-identified fibroblasts were derived from cerebral cortex and white matter from fetal lambs (approximately 120 days gestation) and grown to confluence on glass coverslips in 12 well plates. Levels of prostaglandin $F_{2{\alpha}}$ and the stable hydrolysis product of prostacyclin (i.e., $6-keto-PGF_{1{\alpha}}$) were determined using enzyme immunoassay. Relative amounts of mRNA were determined by in situ hybridization using ovine cDNA for PGHS1. $IL1{\alpha}$ (10 ng/ml) increased mRNA levels over baseline by $62{\pm}19%$ (p＜0.05) at 60 min., $37{\pm}12%$ (NS) at 120 min., and $36{\pm}18%$ (NS) at 240 min (n=12). Levels of $6-keto-PGF_{1{\alpha}}$ were $148{\pm}18%$ pg/ml during baseline, $246{\pm}41%$ pg/ml at 60 min., $248{\pm}40%$ pg/ml at 120 min., and $259{\pm}62%$ pg/ml at 240 min (all p＜0.05) (n=12). $PGF_{2{\alpha}}$ was increased although it wasn't statistically significant. However, $IL1{\alpha}$ decreased $PGE_2$ level significantly (all p＜0.05). PDB $(10^{-6}M)$ increased mRNA levels over baseline by $25{\pm}6%$ after 30 min., $40{\pm}6%$ after 60 min., and $20{\pm}8%$ after 90 min. (n=9) (all p＜0.05). Levels of $6-keto-PGF_{1{\alpha}}$ were $200{\pm}43%$ pg/ml during baseline, $202{\pm}43%$ pg/ml after 30 min. (NS), $268{\pm}58%$ pg/ml after 60 min. (p＜0.05), and $296{\pm}60%$ pg/ml after 90 min. (p＜0.05) (n=9). Levels of $PGF_{2{\alpha}}$ were $178{\pm}26%$ pg/ml during baseline, $300{\pm}30%$ pg/ml after 30 min., $299{\pm}35%$ pg/ml after 60 min., and $355{\pm}32%$ pg/ml after 90 min (all p＜0.05) (n=6). Actinomycin-D (1 mg/ml) prevented increases in mRNA, $6-keto-PGF_{1{\alpha}}$, and $PGF_{2{\alpha}}$ at 60 min. for both $IL1{\alpha}$ and PDB. We conclude that cerebral fibroblasts are avid producers of prostanoids, and that enhanced production of PGHS is responsible for augmented $PGF_{2{\alpha}}$ and prostacyclin production in the presence of an activator of protein kinase C and for decreased $PGE_2$ and increased prostacyclin production in the presence of $IL1{\alpha}$.