• Title/Summary/Keyword: interleukin-2(IL-2)

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기관지천식에서 Interferon-Gamma 치료의 효과 (Efficacy of Interferon-Gamma Treatment in Bronchial Asthma)

  • 김관형;김석찬;김영균;권순석;김치홍;문화식;송정섭;박성학;이충은;변광호
    • Tuberculosis and Respiratory Diseases
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    • 제44권4호
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    • pp.822-835
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    • 1997
  • 연구배경 : 기관지천식의 병태생리중 IgE의 합성 및 조절에 IL-4가 중요한 역할을 하며, IFN-$\gamma$는 이러한 IL-4의 작용을 길항하는 것으로 알려져 있다. 이를 근거로 최근에 IFN-$\gamma$를 아토피 피부염등 IgE가 높은 알레르기성 질환의 치료에 이용하고자 하는 임상적 시도가 있는데, 아직 기관지천식에 대한 임상적 시도는 별로 보고되어 있지 않다. 그러나 IFN-$\gamma$는 in vitro에서 말초혈액 다형핵구나 단핵세포에 의한 독성산화물 생성을 증가시킨다는 보고도 있어, 실제 임상에서 IFN-$\gamma$ 치료의 임상적 효과는 확실하지 않다. 이에 저자들 IL-4 매개성 IgE 생성에 대한 IFN-$\gamma$의 길항작용에 기초하여, IgE가 정상범위보다 높은 기관지천식 환지들에서 in vitro 에서와 같이 in vivo 에서도 IFN-$\gamma$가 IgE 생성을 억제하는지 여부와, 그 결과로 임상적 치료효과를 나타내는지에 대해 관찰하는 한편, 다형핵구의 독성산화물 생성능에 미치는 영향은 in vitro의 경우와 어떻게 다른지에 대해서 관찰하였다. 대상 및 방법 : IgE가 200IU/ml 이상이고 정규적인 부신피질호르몬 치료에 반응을 보이지 않는 기관지천식 환자 50명과 정상인 17명을 대상으로, 혈중 CD23+ B-상층액 발현도, sCD23 농도, T-상층액의 IL-4 activity, 다형핵구에 의한 과산화 음이온 생성능등을 측정한 후, 환자군과 정상군간의 차이를 비교하고, 환자군에 대해서는 상기 검사외에 혈중 IgE 농도 및 histamine $PC_{20}$등을 함께 측정하여 IFN-$\gamma$ 치료전후의 변화를 관찰하였다. IFN-$\gamma$ 치료는 체중당 30,000IU를 매일 4주간 피하주사하였다. 결 과 : 다형핵구의 ${O_2}^-$ 생성능 환자군의 다형핵구는 정상군의 다형핵구에 비해 ${O_2}^-$생성능이 높았다(P<0.05). IFN-$\gamma$ 치료후 추적이 가능했던 환자들에서는 IFN-$\gamma$ 치료후에 다형핵구의 ${O_2}^-$ 생성능이 현저하게 감소하였다(P<0.05). 다형핵구 배양시간에 따라 자연적인 ${O_2}^-$ 생성능 및 PMA 혹은 fMLP 자극에 의한 ${O_2}^-$ 생성능을 관찰하였을 때에도, 배양시간 및 자극제의 종류와 무관하게 IFN-$\gamma$ 치료후가 치료전에 비해 ${O_2}^-$ 생성능이 감소하는 경향을 보였다. IFN-$\gamma$ 치료전의 환자군의 말초혈액내 CD23+ B-상층액의 발현도는 정상군에 비해 현저히 높았으나(P<0.05), 치료후 추적검사가 가능하였던 15명의 환자들에서 치료전후에 의미있는 변화를 나타내지는 않았다. IFN-$\gamma$ 치료전의 환자군의 혈청내 sCD23 농도는 정상군에 비해 다소 높은 경향을 보였으며, 이중 치료 후 추적검사가 가능하였던 17명의 환자들중 11명(64.7%)에서 치료후에 혈청 sCD23 농도가 감소되었다. T-상층액의 IL-4 activity는 정상군에 비해 환자군에서 다소 높은 경향을 보였는데, IFN-$\gamma$ 치료후에는 큰 변화를 보이지 않았다. IFN-$\gamma$ 치료후 혈청 IgE 농도의 추적검사가 시행되었던 환자 15명 중 9명(60%)에서 치료후 혈청 IgE 농도가 유의하게 감소되었다(P<0.05). IFN-$\gamma$ 치료에 따른 기관지과민반웅의 변화는 모두 12명의 환자에서 관찰되었는데, 이중 10명(83.3%)에서 IFN-$\gamma$ 치료후 histamine $PC_{20}$가 유의하게 호전되는 소견을 보여주었다(P<0.05). 결 론 : 이상의 연구결과 IFN-$\gamma$는 IgE가 높은 기관지천식 환자의 치료에 유용할 것으로 추측되며, in vivo에서의 IgE 합성 및 조절기전과 이에 대한 IFN-$\gamma$의 역할을 보다 명확하게 규명하기 위한 노력이 필요할 것으로 생각된다.

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왕느릅나무 껍질 열수 추출물의 마우스에서의 in vivo 면역조절 효과 (Immune-modulation Effect of Ulmus macrocarpa Hance Water Extract on Balb/c Mice)

  • 이인환;권다혜;이선희;이성도;김덕원;이종환;현숙경;김철민;김병우;강경화;황혜진;정경태
    • 생명과학회지
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    • 제24권10호
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    • pp.1151-1156
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    • 2014
  • 약용식물은 염증, 감염증, 암과 같은 질병에 광범위하게 사용되고 있으며, 전통적으로 오래 동안 사용되어 왔다. 왕느릅나무(Ulmus macrocarpa Hance)는 느릅나무의 한 종으로서 중국, 일본을 비롯해 한국 전역에 분포하고 있으며, 줄기와 뿌리의 껍질을 유백피라 하여 한의학에서 피부염, 유방염, 부종 등에 사용하여 왔다. 이 연구의 목적은 유백피의 열수 추출물(Ulmus cortex water extract, UCWE)이 면역조절 기능을 가지고 있는지를 조사하는 것이다. UCWE 식이농도 30 mg/kg, 100 mg/kg, 300 mg/kg의 3개 군으로 나누어 14일 동안 식이한 후 면역반응을 측정하였다. IL-2, IL-12, IFN-${\gamma}$ 의 혈중 농도가 UCWE를 식이한 군에서 유의적으로 증가하였으며, lymphokine activated killer cells (LAK)을 이용한 세포매개 세포독성 시험에서도 정상군에 비해 UCWE를 식이한 군에서 유의적으로 증가하였다. 그러나, 간, 신장, 비장, 흉선의 무게변화는 UCWE를 식이한 군과 정상군과의 차이가 없었다. 이는 300 mg/kg 고농도의 2주간 식이가 장기에 영향을 거의 미치지 않는다는 것을 암시한다고 생각된다. 따라서, UCWE는 내부 장기에는 영향을 주지 않으며 면역기능을 향상시키는 효과를 가진다고 여겨진다.

Enhancement of Antigen Presentation Capability of Dendritic Cells and Activation of Macrophages by the Components of Bifidobacterium pseudocatenulatum SPM 1204

  • HAN Shinha;CHO Kyunghae;LEE Chong-Kil;SONG Youngcheon;PARK So Hee;HA Nam-Joo;KIM Kyungjae
    • Biomolecules & Therapeutics
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    • 제13권3호
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    • pp.174-180
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    • 2005
  • Antigen presenting cells (APCs), dendritic cells (DCs) and macrophages, playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of APC function, we searched for and characterized APC function modulators from natural products. Bifidobacterium pseudocatenulatum SPM1204 (SPM1204) isolated from feces of healthy Korean in the age of 20s was used in this experiment. DCs and macrophages were cultured in the presence of supernatants of SPM 1204 and then examined for their activities for the presentation exogenous antigen in association with major histocompatibility complexes (MHC) and macrophage activation. SPM1204 increased class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells. The RAW 264.7 cell line was used to test the nonspecific effect of immune reinforcement of SPM1204 as a source of biological regulating modulator for the macrophage activation, include nitric oxide (NO) production and cytokine production. Results showed that the production of NO, tumor necrosis factor (TNF)-$\alpha$, interleukin 1 (IL-1)-$\beta$ and morphological changes in macrophages were largely affected by SPM1204 in a dose-dependent manner. Our results demonstrated that SPM1204 promote cross-presentation of dendritic cells as well as the induction of NO, TNF-$\alpha$ production, and activation of macrophage.

Ameliorative effect of myricetin on insulin resistance in mice fed a high-fat, high-sucrose diet

  • Choi, Ha-Neul;Kang, Min-Jung;Lee, Soo-Jin;Kim, Jung-In
    • Nutrition Research and Practice
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    • 제8권5호
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    • pp.544-549
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    • 2014
  • BACKGROUND/OBJECTIVES: Obesity-associated insulin resistance is a strong risk factor for type 2 diabetes mellitus. The aim of this study was to investigate the effect of myricetin on adiposity, insulin resistance, and inflammatory markers in mice with diet-induced insulin resistance. MATERIALS/METHODS: Five-week-old male C57BL/6J mice were fed a basal diet, a high-fat, high-sucrose (HFHS) diet, or the HFHS diet containing 0.06% myricetin or 0.12% myricetin for 12 weeks after a 1-week adaptation, and body weight and food intake were monitored. After sacrifice, serum lipid profiles, glucose, insulin, adipocyte-derived hormones, and proinflammatory cytokines were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was determined. RESULTS: Myricetin given at 0.12% of the total diet significantly reduced body weight, weight gain, and epidydimal white adipose tissue weight, and improved hypertriglyceridemia and hypercholesterolemia without a significant influence on food intake in mice fed the HFHS diet. Serum glucose and insulin levels, as well as HOMA-IR values, decreased significantly by 0.12% myricetin supplementation in mice fed the HFHS diet. Myricetin given at 0.12% of the total diet significantly reduced serum levels of leptin, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) in mice fed the HFHS diet. CONCLUSIONS: These findings suggest that myricetin may have a protective effect against diet-induced obesity and insulin resistance in mice fed HFHS diet, and that alleviation of insulin resistance could partly occur by improving obesity and reducing serum proinflammatory cytokine levels.

Potential Probiotic Properties of Laetoeoeeus laetis NK34 Isolated from Jeotgal

  • Lee, Na-Kyoung;Noh, Ji-Eun;Choi, Gui-Hun;Park, Eun-Ju;Chang, Hyo-Ihl;Yun, Cheol-Won;Kim, Seung-Wook;Kang, Chang-Won;Yoon, Yoh-Chang;Paik, Hyun-Dong
    • Food Science and Biotechnology
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    • 제16권5호
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    • pp.843-847
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    • 2007
  • Strain NK34 was characterized for probiotic use. Strain NK34 was named Lactococcus lactis NK34 based on API 50 CHL kit results and 16S rDNA sequencing. L. lactis NK34 was highly resistant to artificial gastric juice (pH 2.5) and artificial bile acid. Based on results from the API ZYM kit, 4 enzymes were produced. L. lactis NK34 was resistant to all antibiotics tested except for $10\;{\mu}g/mL$ roxithromycin and $10\;{\mu}g/mL$ erythromycin. The cholesterol-lowering effect of L. lactis NK34 was about 46.9%. Concentrations of interleukin $(IL)-1{\alpha}$ in the $20{\times}$ concentrated supernatant of L. lactis NK34 was about 361 pg/mL. L. lactis NK34 was also found to inhibit the growth of colon cancer cells due to MNNG-induced DNA damage. These results demonstrate the potential of L. lactis NK34 as a health-promoting probiotic.

Rehmannia glutinosa Ameliorates Scopolamine-Induced Learning and Memory Impairment in Rats

  • Lee, Bom-Bi;Shim, In-Sop;Lee, Hye-Jung;Hahm, Dae-Hyun
    • Journal of Microbiology and Biotechnology
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    • 제21권8호
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    • pp.874-883
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    • 2011
  • Many studies have shown that the steamed root of Rehmannia glutinosa (SRG), which is widely used in the treatment of various neurodegenerative diseases in the context of Korean traditional medicine, is effective for improving cognitive and memory impairments. The purpose of this study was to examine whether SRG extracts improved memory defects caused by administering scopolamine (SCO) into the brains of rats. The effects of SRG on the acetylcholinergic system and proinflammatory cytokines in the hippocampus were also investigated. Male rats were administered daily doses of SRG (50, 100, and 200 mg/kg, i.p.) for 14 days, 1 h before scopolamine injection (2 mg/kg, i.p.). After inducing cognitive impairment via scopolamine administration, we conducted a passive avoidance test (PAT) and the Morris water maze (MWM) test as behavioral assessments. Changes in cholinergic system reactivity were also examined by measuring the immunoreactive neurons of choline acetyltransferase (ChAT) and the reactivity of acetylcholinesterase (AchE) in the hippocampus. Daily administration of SRG improved memory impairment according to the PAT, and reduced the escape latency for finding the platform in the MWM. The administration of SRG consistently significantly alleviated memory-associated decreases in cholinergic immunoreactivity and decreased interleukin-$1{\beta}$ (IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) mRNA expression in the hippocampus. The results demonstrated that SRG had a significant neuroprotective effect against the neuronal impairment and memory dysfunction caused by scopolamine in rats. These results suggest that SRG may be useful for improving cognitive functioning by stimulating cholinergic enzyme activities and alleviating inflammatory responses.

인간 유래 폐 세포주별 담배연기 분획의 염증 반응 민감도 비교 (Comparison of the Sensitivity of Human Bronchial Epithelial Cells to Cigarette Smoke-induced Inflammatory Responses)

  • 유지혜;손형옥;박철훈;이형석;장미;현학철;신한재
    • 한국연초학회지
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    • 제32권1호
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    • pp.19-27
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    • 2010
  • The aim of this study is to compare the sensitivity of both two NCI-H292 and A549 cell types to acute inflammatory responses induced by cigarette smoke. For this, we treated two kinds of smoke fractions derived from 2R4F reference cigarettes: total particulate matter(TPM) collected onto a Cambridge filter pad and gas/vapor phase(GVP) prepared by bubbling through in buffer solution. When we measured cellular cytotoxicity by neutral red uptake assay after treatment for 24 hours, TPM and GVP induced cytotoxic effect in a dose-dependent manner in the range of 10-$100{\mu}g$/mL and 60-$300 {\mu}g$/mL., respectively, in both cell types without any cellular difference. Additionally, when we examined acute inflammatory responses by analyzing cytokines secreted into culture media including tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-8(IL-8), and transforming growth factor-$\alpha$(TGF-$\alpha$) as well as matrix metalloproteinase-1(MMP-1), the treatment with smoke fractions increased those marker proteins in a dose-dependent manner in NCI-H292. Meanwhile, in A549 cells only MMP-1 was observed to be increased in a dose-dependent fashion. Collectively, our data indicate that NCI-H292 cell type is more sensitive to cigarette smoke-induced inflammatory response than A549 cells. This suggests that NCI-H292 could be useful as an in vitro evaluation tool to assess harmful effects of cigarette smoke.

Fermentation-Mediated Enhancement of Ginseng's Anti-Allergic Activity against IgE-Mediated Passive Cutaneous Anaphylaxis In Vivo and In Vitro

  • Hwang, Seon-Weon;Sun, Xiao;Han, Jun-Hyuk;Kim, Tae-Yeon;Koppula, Sushruta;Kang, Tae-Bong;Hwang, Jae-Kwan;Lee, Kwang-Ho
    • Journal of Microbiology and Biotechnology
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    • 제28권10호
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    • pp.1626-1634
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    • 2018
  • Ginseng (the root of Panax ginseng Meyer) fermented by Lactobacillus plantarum has been found to attenuate allergic responses in in vitro and in vivo experimental models. Ginseng has been reported to also possess various biological functions including anti-inflammatory activity. The present study was aimed at comparing the anti-allergic effect of ginseng and fermented ginseng extracts on IgE-mediated passive cutaneous anaphylaxis in vitro in a murine cell line and in vivo in mice. Fermented ginseng extract (FPG) showed higher inhibitory effect against in vitro and in vivo allergic responses when compared with ginseng extract (PG). The secretion of ${\beta}$-hexosaminidase and interleukin (IL)-4 from the IgE-DNP-stimulated RBH-2H3 mast cells were significantly (p < 0.05) inhibited by FPG treatment, and this effect was concentration-dependent. Further, MKK4 activation and subsequent JNK phosphorylation were attenuated by FPG treatment. The inhibitory effect of FPG on the in vitro allergic response was verified in vivo against IgE-DNP-induced passive cutaneous anaphylaxis in a mouse model. These data indicated that the fermentation of ginseng with L. plantarum enhanced its anti-allergic effects both in vitro and in vivo. We predict that compositional changes in the ginsenosides caused by the fermentation may contribute to the change in the anti-allergic effects of ginseng. The results of our study highlight the potential of the use of FPG as a potential anti-allergic agent.

Oncostatin M이 피부섬유모세포의 증식과 기질생성에 미치는 영향 (Effect of Oncostatin M on Proliferation and Matrix Synthesis of Dermal Fibroblasts)

  • 전경욱;임형우;한승규;김우경
    • Archives of Plastic Surgery
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    • 제35권2호
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    • pp.115-120
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    • 2008
  • Purpose: Oncostatin M(OSM) is a multifunctional cytokine that belongs to the interleukin(IL)-6 family. Although there have been a number of studies that focused on the role and mechanism of OSM in various organs and tissues, there are few reports on its effect on wound healing. The final purpose of this project is to evaluate the effect of OSM on wound healing. This pilot study was designed to investigate the effect of OSM on proliferation and matrix synthesis of human dermal fibroblasts, which are the major components of the wound healing. Methods: Excess skin that was obtained from patients who underwent skin grafts, was used for this study. From this material, fibroblasts were isolated and cultured. The cultured fibroblasts were treated with one of four concentrations of OSM. The OSM concentrations used were 0, 50, 100, and 200 ng/ml, respectively. After the OSM treatment, cell proliferation was determined by the MTT assay, collagen synthesis by the C1CP method, GAG levels by the Blyscan Dye method. The parameter levels of each group were compared. Results: OSM treatment increased all the components tested in the study. In particular, cell proliferation, GAG synthesis demonstrated statistically significant increases(p<0.05 in the Mann-Whitney U-test). The highest increase in all the components was obtained at a 100 ng/ml concentration of OSM.Conclusion: The results of the present study indicate that OSM stimulates proliferation and matrix synthesis of human dermal fibroblast and the optimal concentration for wound healing is 100 ng/mL.

Ginsenosides Inhibit HMGB1-induced Inflammatory Responses in HUVECs and in Murine Polymicrobial Sepsis

  • Lee, Wonhwa;Ku, Sae-Kwang;Jeong, Tae Cheon;Lee, Sangkyu;Bae, Jong-Sup
    • Bulletin of the Korean Chemical Society
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    • 제35권10호
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    • pp.2955-2962
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    • 2014
  • Asian ginseng is used as a treatment for cardiovascular diseases, ischemia, and cancers. High mobility group box 1 (HMGB1) protein acts as a late mediator of severe vascular inflammatory conditions. However, the effect of ginsenosides from Asian ginseng on HMGB1-induced inflammatory responses has not been studied. We addressed this question by monitoring the effects of ginsenoside treatment on lipopolysaccharide (LPS) and cecal ligation and puncture (CLP)-mediated release of HMGB1, and HMGB1-mediated regulation of proinflammatory responses. Ginsenoside treatment suppressed LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangements. Ginsenosides also inhibited HMGB1-mediated inflammatory responses. In addition, ginsenosides inhibited the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and activation of protein kinase B (Akt), nuclear factor-${\kappa}B$ (NF-${\kappa}B$), and extracellular-regulated kinases (ERK) 1/2 by HMGB1. Ginsenosides also decreased CLP-induced release of HMGB1, production of interleukin (IL) $1{\beta}/6$, and mortality. These results suggested that ginsenosides may be potential therapeutic agents for treatment of vascular inflammatory diseases through inhibition of the HMGB1 signaling pathway.