• Title/Summary/Keyword: Interleukin-$1{\alpha}$

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Detection of TNF-alpha in Serum as the Effect of Corticosteroid to the Myocardial Protection in Cardiopulmonary Bypass (체외순환시 스테로이드의 심근보호효과에 관한 혈청내 TNF-alpha 측정의 의의)

  • 최영호;김욱진;김태식;조원민;김학제
    • Journal of Chest Surgery
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    • v.31 no.5
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    • pp.502-508
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    • 1998
  • Proinflammatory cytokines such as tumor necrosis factor-$\alpha$(TNF-$\alpha$) have been implicated in myocardial and organ dysfunction associated with postperfusion syndrome. We tested the hypothesis that cytokine productions are depressed by preoperative cortiosteroid injection for cardiopulmonary bypass(CPB) and the postoperative courses will be better than without steriod pretreated cases. Cardiac surgery was performed in randomized blind fashion for 20 patients from June 1996 to September 1996. In the steroid group(n=10), corticosteroid(dexamethasone 1 mg/kg) was injected 1 hour before anesthetic induction, but in the control group(n=10), nothing was injected. Each of groups were sampled 11 times as scheduled for TNF-$\alpha$ bioassays. We have checked EKG, cardiac enzymes(CPK, LDH with isoenzyme), WBC count preoperative day, one day and three days after operation. Viatal signs were continuously monitored for three postoperaive days. In the postoperative period three patients in the control group had elevated body temperature and four patients had hypotension that required considerable intravenous fluid administration. But steroid injected patients showed normal body temperture and acceptable blood pressures without supportive treatment. CPK enzymes rose in control group higher than steroid group at postoperative 1st and 3rd day(CPK; 1122$\pm$465 vs 567$\pm$271, 864$\pm$42 vs 325$\pm$87), and CPK-MB enzymes rose in control group higher than steroid group at postoperative 1st day(106.4$\pm$115.1 vs 29.5$\pm$22.4)(P=0.02). Arterial tumor necrosis factor-$\alpha$ rose during cardiopulmonary bypass, peaking at 5 minutes before the end of aortic cross clamping(ACC-5min) in steroid group(11.9$\pm$4.7 pg/ml), and 5 minutes before the end of cardiopulmonary bypass(CPB-5min) in control group(22.3$\pm$6.8 pg/ml). The steroid pretreated patients had a shorter period of time in respirator suport time, ICU stay day, hospital admission day. We conclude that corticosteroid suppress cytokine production during and after cardiopulmonary bypass, and may improve the postoperative course through inhibition of reperfusion injury such as myocardial stunning and hemodynamic instability.

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Effects of Ginsenoside Rg3 on Early-stage Inflammatory Response in Spinal Cord Compression of Rodents (Ginsenoside Rg3이 흰쥐 척수압박손상의 초기 염증반응에 미치는 영향)

  • Jeong, Beoul;Lee, Jong-Soo
    • Journal of Korean Medicine Rehabilitation
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    • v.23 no.2
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    • pp.1-15
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    • 2013
  • Objectives : In present study, we investigated the effects of ginsenoside Rg3 on early-stage inflammatory response in spinal cord compression of rodents. Methods : Spinal cord injury(SCI) was induced by a vascular clip method(30 g, 5 min) on the spinal cord of mice. Rg3 was treated orally at 1 hour prior to the SCI induction. Messenger ribonucleic acid(mRNA) expression of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), interleukin-1${\beta}$(IL-1${\beta}$), interleukin-6(IL-6) and cyclooxygenase-2(COX-2) was measured by the real-time polymerase chain reaction(RT-PCR). Microglia in the spinal cord tissue, neurophils and COX-2 in the peri-lesion and inducible nitric oxide synthase(iNOS) expression in the ventral horn of SCI induced rats were measured by immunohistochemical stain. Results : 1. Rg3 significantly reduced the mRNA expression of TNF-${\alpha}$, IL-1${\beta}$, and COX-2 in the spinal cord tissue compared with SCI group(p<0.05, p<0.01). 2. Rg3 significantly reduced the total number of activated microglia and proportion of phagocytic form in the total activated microglia compared with SCI group(p<0.05, p<0.01). 3. Rg3 significantly reduced myeloperoxidase(MPO) positive neurophil in the peri-lesion compared with SCI group(p<0.05). 4. Rg3 reduced the COX-2 expression in the tissue and motor neurons compared with SCI group. 5. Rg3 significantly reduced iNOS positive motor neurons in the ventral horn compared with SCI group(p<0.01). Conclusions : In conclusion, we demonstrated at first that treatment of ginsenoside Rg3 could reduce significantly the levels of inflammatory mediators in a spinal cord compression model of rodents. Therefore, these results suggested that ginsenoside Rg3 may be a useful antimiflamatory therapeutic candidate for SCI.

NMAAP1 Expressed in BCG-Activated Macrophage Promotes M1 Macrophage Polarization

  • Liu, Qihui;Tian, Yuan;Zhao, Xiangfeng;Jing, Haifeng;Xie, Qi;Li, Peng;Li, Dong;Yan, Dongmei;Zhu, Xun
    • Molecules and Cells
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    • v.38 no.10
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    • pp.886-894
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    • 2015
  • Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-$Gu{\acute{e}}rin$) activates disabled $na{\ddot{i}}ve$ macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). 1 The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-${\alpha}$), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-$1{\beta}$), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-${\beta}$) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.

Effect of Doenjang with Black Soybean on Cytokine Production and Inhibition of Tumor Metastasis (검정콩 된장의 사이토카인 생성 및 종양전이 억제에 미치는 영향)

  • Lim, Sun-Young;Park, Kun-Young;Bae, Myung-Suk;Kim, Kwang-Hyuk
    • Journal of Life Science
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    • v.19 no.2
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    • pp.264-270
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    • 2009
  • We investigated the effect of black soybean and doenjang with black soybean on production of cytokines including interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) compared with yellow soybean and doenjang with yellow soybean. We also determined inhibitory effect of two types of soybeans and doenjang on tumor metastasis produced by colon 26-M3.1 carcinoma cells. The cytokine productions of mouse splenocytes increased by the exposure of lipopolysaccharide (LPS, 1 ${\mu}g$/ml) compared to without treatment of LPS. The LPS-induced IL-2 production was highest in the black soybean methanol extract, while the methanol extract from black soybean doenjang fermented for 2 mo showed the higher levels of IL-2 without LPS (p<0.05). In case of LPS-induced IL-6 production, the methanol extracts from control, yellow soybean, black soybean doenjang fermented for 2 and 7 mo showed higher levels of IL-6 compared to those of black soybean, and yellow soybean doenjang fermented for 2 mo (p<0.05). The methanol extract of black soybean doenjang fermented for 2 mo showed significantly higher levels of TNF-${\alpha}$ in both with and without LPS (p<0.05). In experiment of tumor metastasis, the treatment (1 mg/mouse) of methanol extract from black soybean doenjang fermented for 7 mo inhibited tumor metastasis by 50% and had the highest inhibitory effect among other samples (p<0.05). From these results, doenjang manufactured with black soybean modulated the production of cytokine and showed anticancer effect, suggesting that this effect was increased with increased periods of fermentation.

Effects of Gagamdokhwalgisang-Tang(GD;加減獨活奇生湯) on the Morphometric Changes of Femur and the Factors Related with Bone Metabolism in Ovariectomized Rats (가감독활지생탕(加減獨活奇生湯)이 난소적출 흰쥐 대퇴골의 형태계측학적 변화 및 골대사 관련인자에 미치는 영향)

  • Moon, Hyon-Ju;Lim, Eun-Mee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.19 no.1
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    • pp.47-68
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    • 2006
  • Purpose : This study was carried out to investigate the effects of Gagamdokhwalgisang-Tang on the morphometric changes of femur, and on the hormones and cytokines associated with bone metabolism in overiectomized rats. Methods : Twenty-four female Sprague-Dawley rats were divided into sham operated group(normal) ovariectomized group(control), and treated with extract of GD group(treated). Each group was evaluated the changes of body weight at 0, 3, 6, 8 weeks after ovariectomy. Morphometric analysis(femur weight, femur/body weight ratio, femur ash weight femur ash/body weight ratio cross sectional area of compact bone and concellous bone of femur) and histopathological examination were performed at 8 weeks after ovariectomy. Estrogen, Alkaline Phosphatase(ALP) and cytokine(Tumor necrosis $factor-{\alpha}$, $Interleukin-l{\beta}$, Inerleukin-6) assay were performed at 8 weeks after ovariectomy. Results : 1. The body weight of control and treated group was significantly increased(p<<0.001) compared with the normal group at 8 weeks. 2. The femur weight and femur/body weight ratio of treated group were significantly increased(p<<0.05, p<<0.01) compared with the control group at 8 weeks. 3. The femur ash weight showed no significantly different changes, but femur ash/body weight ratio of treated group was significantly increased(p<<0.05) compared with the control group at 8 weeks. 4. In the cross sectional area of cancellous bone of femoral body, the treated group was significantly increased(p<<0.001) compared with the control group at 8 weeks. 5. The serum estrogen level of treated group showed no significantly different changes compared with the control group at 8 weeks. 6. The serum ALP activity of treated group was significantly decreased(p<<0.01) compared with the control group at 8 weeks. 7. The serum Tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ level of treated group was significantly decreased(p<<0.05) compared with the control group at 8 weeks. 8. The serum $Interleukin-l{\beta}(IL-1{\beta})$ level of treated group was significantly decreased(n<<0.001) compared with the control group at 8 weeks. 9. The serum Interleukin-6(IL-6) level of treated group was significantly decreased(P<<0.01)compared with the control group at 8 weeks. Conclusion : These results indicate that GD inhibits bone resorption in ovariectomized rats. And the major inhibitory mechanism may be related to the inhibitory effects of GD on the secretion of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 in the pathogenesis of osteoporosis in estrogen deficient rats.

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Microarray Analysis of Gene Expression in Chondrosarcoma Cells Stimulated with Bee Venom (봉독이 연골육종세포의 유전자 발현에 미치는 영향에 대한 Microarray 연구)

  • Yin, Chang-Shik;Koh, Hyung-Gyun
    • Journal of Pharmacopuncture
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    • v.7 no.2
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    • pp.19-28
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    • 2004
  • 봉독은 관절염 치료를 비롯한 여러 질환에 그 응용범위가 넓어지고 있으며 기전규명과 새로운 치료효과 개발을 위한 연구가 필요하다. 연골의 파괴는 진행된 각종 관절병증의 공통 병리기전이며 연골세포의 기능이상은 이 기전에 중요한 의미를 지닌다. 사람 연골세포의 특성을 유지하고 있는 HTB-94 연골육종세포를 배양하고 봉독을 처치했을 때의 유전자 발현양상을 microarray를 이용하여 관찰하였다. 대조군에 비해 4배 이상 발현의 차이가 있는 경우를 유의한 것으로 보았을 때 microarray의 344개 유전자중 봉독처치시 발현이 증강되는 유전자는 없었으며 발현이 억제되는 유전자는 interleukin 6 receptor, interleukin 1 alpha, tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 1, tumor necrosis factor (ligand) superfamily, members 4, 8 and 12, and caspases 2, 6, and 10등 35개가 관찰되었다. Microarray를 통한 유전자발현 분석을 통해 관절염에 대한 봉독치료의 기전을 시사하는 유용한 자료를 얻을 수 있었으며 앞으로 보다 넓은 범위에 대한 연구가 필요할 것이다.

The Effect of Barbaloin on LPS-stimulated Inflammatory Reaction in Mice Peritoneal Macrophages

  • Jeon, Yong-Deok;Lee, Jong-Hyun
    • Korean Journal of Plant Resources
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    • v.30 no.3
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    • pp.280-286
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    • 2017
  • Barbaloin is a major component of Aloe vera, which has been used for a laxative. Also, barbaloin is C-glucoside of aloe emodin anthrone which is founded in Aloe vera. Barbaloin has varieties of pharmacological activity such as inhibitory effects on inflammation, histamine release, cancer and microbial infection. But the effect of barbaloin on lipopolysaccharide (LPS)-stimulated macrophages has not been understood. In this study, we evaluated the effects of barbaloin against LPS-stimulated production of nitric oxide (NO), inflammatory cytokines and MAPKs activation in macrophage. We treated barbaloin (0.1, 1, 10, $100{\mu}M$) in LPS-stimulated mice peritoneal macrophage. Our results showed that barbaloin significantly inhibited production of NO and cytokines of tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-6, interleukin $(IL)-1{\beta}$ in LPS-stimulated peritoneal macrophage. Moreover, barbaloin inhibited the phosphorylation of ERK and JNK in a dose dependent manner. These results indicated that barbaloin could be useful for inflammatory diseases.

The role of myokine(interleukin) and exercise for the prevention of scarcopenia and anti-inflammation (근감소 및 염증 예방을 위한 운동과 인터루킨(IL-interleukin)의 역할)

  • Byun, Yong-Hyun;Park, Woo-Young
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.2
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    • pp.509-518
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    • 2018
  • The purpose of this study was myokine product and role with physical activity and literature review. There is accumulating epidemiological evidence that a physically active life plays an independent role in the protection against type 2 diabetes, cardiovascular disease, colon cancer, dementia and even depression. And myokine has been regarded an important factor of exercise training and brain growth factor for the prevention of Alzheimier's disease. During exercise the release of anti-inflammatory myokine from contracting muscle controled the metabolic response, and IL-4, IL-6, IL-7, IL-10, and IL-15 controled muscle hypertrophy, myogenesis and angiogenenesis. IL-6 promoted the lipid metabolism through AMPK activation. IL-1Ra, IL-10 and sTNF-R inhibited $TNF-{\alpha}$ as the pro-inflammatory cytokine. IL-15 increased the releasing volume from contracting muscle, and promoted the anabolic factor of muscle growth. IL-7 and IL-8 activated the angiogenesis through the more activation of C-X-C receptor signal transmission.

Mycobacterium tuberculosis-induced Expression of Interleukin-1 Beta is Mediated Via Protein Kinase C Signaling Pathway

  • Cho, Jang-Eun;Lee, Kyung-Hong;Son, Sin-Jee;Park, Sang-Jung;Lee, Hye-Young;Kim, Yoon-Suk
    • Biomedical Science Letters
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    • v.16 no.2
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    • pp.119-122
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    • 2010
  • Interleukin-1${\beta}$ $(IL-1{\beta})$ is one of the key proinflammatory cytokines and it plays an important role for the antimycobacterial host defense mechanisms. In this study, we examined Mycobacterium tuberculosis (MTB)-stimulated induction of IL-1${\beta}$ and evaluated the associated signal transduction pathways. In PMA-differentiated THP-1 cells, MTB infection increased mRNA expression of IL-$1{\beta}$ in a dose-dependent manner. The expression of IL-1${\beta}$ mRNA began to be induced at 1.5 h after infection, and induced expression of IL-1${\beta}$ was retained for 48 h after MTB infection. The increase in expression of IL-1${\beta}$ caused by MTB was reduced in cells treated with Ro-31-8425 (an inhibitor of PK$C{\alpha}$, ${\beta}I$, ${\beta}II$, ${\gamma}$, ${\varepsilon}$) or PD98059 (an inhibitor of MEK1), meanwhile, pre-treatment with $G\ddot{o}6976$ (an inhibitor of $Ca^{2+}$ dependent PK$C{\alpha}$ and PK$C{\beta}I$) or Rottlerin (an inhibitor of PK$C{\delta}$) has no effect on MTB-induced expression of $IL-1{\beta}$ mRNA. These results show that the expression of $IL-1{\beta}$ mRNA caused by MTB may be mediated via MEK1 and PKC isoforms including PK$C{\beta}II$, $PKC{\gamma}$, or $PKC{\varepsilon}$. Further studies are required to determine whether other PKC isoforms $(PKC {\eta},\;{\theta},\;{\varepsilon},\;and\;{\lambda}/{\iota})$, except $PKC{\delta}$, $PKC{\alpha}$, and $PKC{\beta}I$, are also involved in $IL-1{\beta}$ mRNA expression after mycobacterial infection.

Anti-inflammatory Activity of the Undaria pinnatifida Water Extract (미역(Undaria pinnatifida) 물 추출물의 염증 억제 활성)

  • Jeong, Da-Hyun;Kim, Koth-Bong-Woo-Ri;Kang, Bo-Kyeong;Jung, Seul-A;Kim, Hyun-Jee;Jeong, Hee-Ye;Bark, Si-Woo;Ahn, Dong-Hyun
    • Journal of Applied Biological Chemistry
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    • v.55 no.4
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    • pp.221-225
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    • 2012
  • The anti-inflammatory effects of Undaria pinnatifida water extract (UPWE) were investigated using lipopolysaccharide-induced inflammatory response in this study. To examine the potential anti-inflammatory properties of UPWE, the cell proliferation, nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-${\alpha}$) and IL-$1{\beta}$ were measured. As a result, there was no cytotoxicity in the macrophage proliferation treated with UPWE compared to the control. NO levels decreased with increasing concentration of UPWE. Moreover, the secretion of IL-6, TNF-${\alpha}$ and IL-$1{\beta}$ were suppressed in a dose-dependent manner, and IL-6 inhibition activities were over 50% at 0.1%. These results suggested that UPWE may have significant effects on inflammatory factors and be a potential anti-inflammatory therapeutic materials.