• 제목/요약/키워드: sIL-2R

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Inflammatory cytokines in midbrain periaqueductal gray contribute to diabetic induced pain hypersensitivity through phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

  • Guo, Mochi;Jiang, Zongming;Chen, Yonghao;Wang, Fei;Wang, Zhifeng
    • The Korean Journal of Pain
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    • 제34권2호
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    • pp.176-184
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    • 2021
  • Background: Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG. Methods: Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors. Results: Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1β, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor [TNFR] subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling. Conclusions: Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.

수용성 트랜스페린 수용체의 농도와 염증 인자와의 관련성에 관한 연구 (Correlaton between soluble transferrin receptor concentration and inflammatory markers)

  • 김소영;손명희;염정숙;박지숙;박은실;서지현;임재영;박찬후;우향옥;윤희상
    • Clinical and Experimental Pediatrics
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    • 제52권4호
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    • pp.435-440
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    • 2009
  • 서 론 : 수용성 트랜스페린 수용체(sTfR)는 적혈구 조혈 및 철분 상태를 나타내는 지표로 이용된다. 본 연구는 급성 염증물질과 sTfR 농도와의 관계를 밝히고, 철분 부족 상태와 염증으로 인한 빈혈을 감별하는데 sTfR 농도가 유용한지를 알아보고자 한다. 방 법 : 2000년 1월부터 2006년 6월까지 경상대학교 병원 소아청소년과를 내원한 2세 미만의 영유아 144명을 대상으로 이들의 Hb, MCV, 페리틴, 수용성 트랜스페린 수용체, 염증인자[CRP, IL-6, ANC]를 측정하였다. Hb 11 g/dL 미만이고 페리틴 12 ug/L 미만인 철결핍 빈혈 환아는 조사에서 제외하였다. 결 과 : 전체 환자군에서 sTfR 농도는 Hb, 페리틴, MCV, ANC와 유의한 음의 상관관계를 보였고 CRP, IL-6 와는 상관관계를 보이지 않았다. 다중 선형 회귀 분석 시 IL-6 (r=0.078, P=0.043)는 sTfR 농도와 양의 상관관계를 보였고, ANC (r=-0.117, P=0.033), MCV (r=-0.027, P=0.009)는 음의 상관관계를 보였다. 결 론 : 영유아에서 sTfR 농도는 염증 상태에 따라 영향을 받을 수 있으므로 급성 감염에 의한 빈혈과 철결핍성 빈혈의 감별진단을 위해서 sTfR 농도를 단독으로 사용하는데 제한점이 있다.

인삼 사포닌에서 Ginsenoside-$Rg_2$와 -$Rg_3$의 이성질체인 20(R&S) Prosapogenin들의 역상 고속 액체 크로마토그래피에 의한 분리 (Separation of 20(R&S) Prosapogenin Isomers of Ginsenoside-$Rg_2$ and -$Rg_3$ from Ginseng Saponins by Reversed-Phase High Performance Liquid Chromatography)

  • 정승일;김천석;이용구;이호섭;김일광
    • 분석과학
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    • 제11권5호
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    • pp.404-408
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    • 1998
  • Using a reversed-phase high performance liquid chromatography, the separation of 20(S)-, 20(R)-prosapogenin stereo-isomers of ginsenoside-$Rg_2$ and of ginsenoside-$Rg_3$ in ginseng saponins has been carried out with binary solvent system. The optimum conditions for the isomer separation are as following: Nova-$Pak^{(R)}C_{18}$ (Waters, $3.9{\times}150mm$) column, $CH_3CN/CH_3CN$ (100:8, v/v) binary solvent system and the flow rate was 1.7 mL/min. The stereoisomers were separated with change of the mixture ratio of the solvent system, the solvent elution by gradient program, and then detected at 203 nm of UV detector. The simultaneous separation of mixture that were the $Rg_2$, $Rg_3$ isomers was easily performed in nonpolar solvent for $Rg_2$, polar solvent for $Rg_3$ at the same optimum conditions.

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미세먼지 유도 기도염증에 대한 배암차즈기 추출물의 호흡기 보호 효과 (Respiratory Protective Effect of Salvia plebeia R. Br. Extracts against Ambient Particulate Matter-induced Airway Inflammation)

  • 송형우;지건영;김복규;양원경;한창균;신한재;박양춘;황지숙;강형식;김승형
    • 한국약용작물학회지
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    • 제25권5호
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    • pp.269-281
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    • 2017
  • Background: Small particles increase airway inflammation upon reaching the alveoli. Here, we investigated the protective or therapeutic effects of Salvia plebeia R. Br. (SP_R) extracts on airway inflammation. Methods and Results: To investigate the anti-inflammatory activity of SP_R extracts, we measured their inhibitory effect on the production of reactive oxygen species (ROS) expression of inflammatory mediators, and immune cell infiltration in MH-S alveolar macrophage cells and in the ambient particulate matter (APM)-exposed airway inflammation mice model. The SP_R extracts inhibited the production of ROS and expression of IL-4, IL-10, IL-15, and IL-17A mRNA in APM-stimulated MH-S cells. Oral administration of SP_R extracts suppressed APM-induced inflammatory symptoms, such as high alveolar wall thickness, excess collagen fibers, decreased mRNA expression of chemokines (Ccr9, Ccl5, Ccr3), inflammatory cytokines (IL-15, TNF-${\alpha}$), and IL-4 Th2 cytokine in the lung. The SP_R extracts also inhibited ROS production, granulocyte ($CD11b^+Gr-1^+$) infiltration, IL-17A, TNF-${\alpha}$, macrophage inflammatory protein (Mip-2), and chemokine (C-X-C motif) ligand 1 (Cxcl-1) production in the airway. The specific compounds in the SR-R extracts that mediate the anti-inflammatory effects were identified. Conclusions: In this study, SP_R extracts effectively inhibited airway inflammatory responses, such as ROS production and granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines.

Evaluation of Anti-Colitic Effect of Chung-Jang-Hwan (C-mix) in Mice

  • Lee, Ho-Yong;Ahn, Young-Tae;Park, Se-Hoon;Ahn, Young-Min;Shim, Jae-Jung;Lee, Jung-Hee;Lee, Jeong-Sang;Surh, Young-Joon;Huh, Chul-Sung;Kim, Dong-Hyun
    • Biomolecules & Therapeutics
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    • 제19권1호
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    • pp.52-58
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    • 2011
  • The inhibitory effect of Chung-Jang-Hwan (C-mix) consisted of Geranium nepalense subsp. thunbergii, Saururus chinensis, and Rubus coreanus were investigated in dextran sulfate sodium (DSS)-induced colitic mice by microarray analysis. Treatment with Cmix improved colitic symptoms, including colon shortening and myeloperoxidase activity. Treatment with DSS alone upregulated the expression levels of inflammation-related genes, including IL-$1\beta$, IL-6, CCL2, CCL4, CCL5, CCL7, CCL8, CCL24, CXCL1, CXCL2, CXCL5, CXCL9 and CXCL10, and other colitis-related genes such as COX-2, PAP, MMP family, S100a8, S100a9 and DEFA1 in mice. However, treatment with C-mix inhibited the expression levels of inflammation-associated genes induced by DSS. The increased expression levels of COX-2 and IL-$1\beta$, representative inflammatory genes, were confirmed by a quantitative realtime polymerase chain reaction analysis. These results indicate that C-mix may ameliorate colitis by the inhibitory regulation of inflammation-associated genes.

일부 살충해독유(殺蟲解毒類) 한약의 Staphylococcus aureus에 대한 시험관 내 항균 및 항염 효과 (In Vitro Anti-bacterial and Anti-inflammatory Effects of Six Types of Herb Aqueous Extracts)

  • 장세란;김동철
    • 대한한방부인과학회지
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    • 제27권1호
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    • pp.81-100
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    • 2014
  • Objectives: The object of this study was to observe the in vitro anti-bacterial and anti-inflammatory effects of six single aqueous herbal extracts-Quisqualis Fructus (QuF), Meliae Cortex (MeC), Arecae Semen (ArS), Crassirhizomae Rhizoma (CrR), Ulmi Pasta Semen(UlS), Torreyae Semen(ToS)- against Staphylococcus aureus (S. aureus) and Lipopolysaccharide(LPS)-activated Raw 264.7 cells. Methods: Anti-bacterial activities against S. aureus of aqueous extracts of QuF, MeC, ArS, CrR, UlS and ToS were detected using standard agar microdilution methods. In addition, the effects on the cell viability, prostaglandin $E_2$ ($PGE_2$), nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$ and IL-6 productions of LPS activated Raw 264.7 cells were detected. The anti-bacterial and anti-inflammatory effects were respectively compared with lincomycin and piroxicam. Results: Minimal Inhibition Concentration (MIC) of aqueous extracts of QuF, MeC, ArS, CrR, UlS and ToS against S. aureus was respectively detected $5.625{\pm}4.075$ (3.125~12.500), $0.332{\pm}0.273$ (0.098~0.782), $1.094{\pm}0.428$ (0.782~1.563), $2.969{\pm}2.096$ (0.782~6.250), $9.375{\pm}4.419$ (3.125~12.500)>25 mg/ml. MIC of lincomycin was detected as $0.469{\pm}0.297$ (0.195~0.782) ${\mu}g/ml$ at same conditions. In addition, $ED_{50}$ against LPS-induced cell viabilities and cytokine releases of QuF, MeC, ArS, CrR, UlS and ToS was as follows - Cell viability: 66.370, 2.908, 1.747, 259.553, 18.150 and 34.160 mg/ml; NO production: 389.486, 0.294, 0.138, 523.060, 45.363 and 49.327 mg/ml; $PGE_2$ production: 114.271, 0.223, 0.046, 243.078, 8.829 and 28.947 mg/ml; TNF-${\alpha}$ production: 406.288, 0.343, 0.123, 9404.227, 125.406 and 140.775 mg/ml; IL-$1{\beta}$ production: 117.178, 0.135, 0.019, 237.451, 7.923 and 19.418 mg/ml; IL-6 production: 31.261, 0.105, 0.055, 128.434, 2.290 and 3.745 mg/ml. ED50 of piroxicam against LPS-induced cell viabilities, NO, $PGE_2$, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 were detected as 35.179, 6.552, 1.162, 7.273, 7.101 and $5.044{\mu}g/ml$, respectively at same conditions. Conclusions: All six single aqueous herbal extracts showed anti-bacterial effects against S. aureus, in the order of MeC, ArS, CrR, QuF and UlS aqueous extracts except for ToS; they did not showed any anti-bacterial effects (MIC>25 mg/ml). They also showed anti-inflammatory effects against LPS-activated Raw 264.7 cells in the order of ArS, MeC, UlS, ToS, QuF and CrR aqueous extracts. It means that the ArS and MeC will be showed favorable potent anti-bacterial and related anti-inflammatory effects.

Interleukin-2 Inhibits Secretin-Induced Bile Secretion in Cholangiocytes

  • Ko, Yoo-Seung;Hwang, Seock-Yeon;Park, Jae-Seung
    • 대한의생명과학회지
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    • 제19권2호
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    • pp.158-163
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    • 2013
  • Cholestatic liver is associated with hepatic inflammation and elevated proinflammatory cytokines. Recent studies indicate that certain cytokines can modulate bile secretion. In the present study, we have examined the role of interleukin (IL-2) on the bile secretion by a combination of study models. To examine the relevance of IL-2 on bile secretion, the expression of IL-2 and IL-2 receptor (IL-2R) of isolated normal and bile duct ligated (BDL) rats cholangiocytes was first measured by RT-PCR. In BDL rats, the expression of IL-2 and IL-2R was significantly increased compared with normal rats. To study the effect of IL-2 on bile secretion, bile flow was measured in normal and BDL rats. At the level of cholangiocytes, secretory responses of isolated bile duct unit (IBDU)s were quantified by videomicroscopy. The administrations of IL-2 had no significant effect on basal bile secretion in normal and BDL rats. There was no significant effect of IL-2 on basal bile ductular secretion as evidenced by no significant difference in luminal area of the IBDUs perfusedwith 100 pM of IL-2 from those of albumin carrier control. However, the secretin-stimulated bile ductular secretion was significantly (P < 0.01) inhibited by $34{\pm}4%$ (normal, n = 12), $21{\pm}5.3%$ (BDL 2 wk, n = 12) and $15{\pm}5.2%$ (BDL 4 wk, n = 12) with the co-administration of IL-2. As with other cytokines, physiologically relevant concentration of IL-2 can significantly inhibit secretin-stimulated bile ductular secretion. These findings support the important roles of cytokines in modulating bile secretion and may contribute to the cholestasis seen in cholestatic liver diseases.

Methyl Methanesulfonate 에 의한 DNA 回復合成에 미치는 Thymidine 相似체體의 感受性 효과 (Sensitization Effects of Thymidine Analogs on Methyl Methanesulfonate Induced DNA Repair synthesis)

  • Park, Sang-Dai;Um, Kyung-Il
    • 한국동물학회지
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    • 제18권3호
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    • pp.131-140
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    • 1975
  • HeLa $S_3$ 細胞를 재료로 DNA 回復合成에 미치는 Methyl methanesulfonate(MMS)와 thymidine 相似體(BUdR, IUdR)의 이중효과를 농도와 시간변화에 따라 $^3 H$-thymidine 처리에 의한 自記放射法으로 조사한 결과는 다음과 같다. 1. MMS를 단독 처리한 경우 標識細胞의 빈도는 MMS의 농도 증가에 따라 증가한다. 이는 DNA 回復合成을 한 細胞의 빈도가 증가한 결과로 細胞當 Grain 數의 증가현상과 일치한다. 시간변화에 따른 DNA 回復合成은 MMS와 $^3 H$-thymidine 처리후 2$\\sim$3시간에 최대증가율을 보인다. 2. BUdR 또는 IUdR의 단독처리후 DNA 回復合成을 일으키지 않는다. 그러나 MMS와 이중 처리할 경우 標識細胞, DNA 回復合成細胞, 그리고 細胞當 Grain 數는 MMS 단독 처리한 경우보다 훨씬 증가한다. 따라서 이 두 물질은 MMS에 의한 DNA 回復合成을 효과적으로 증가시키는 感受性物質로 작용함이 판명되었다.

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국내 갈매나무과 13종에 대한 부위별 물 추출물의 면역 증진 활성 (Immune-enhancing Activity of Water Extracts for Each Part of 13 Species (Rhamnaceae) in Korea)

  • 정대희;최민영;박광훈
    • 한국자원식물학회지
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    • 제37권1호
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    • pp.1-10
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    • 2024
  • 본 연구에서는 국내 자생하고 있는 갈매나무과 식물 13종에 대한 부위별(잎, 가지, 열매) 물 추출물의 NO 생성능을 통하여 면역증진 활성을 측정하여 기능성을 검토하였다. 망개나무, 헛개나무, 까마귀베개, 산황나무, 갈매나무, 참갈매나무, 상동나무 등에서 50% 이상 NO 생성능을 보여줌으로써 대식세포 활성화를 검증하였다. 또한 PCR 전기영동을 통하여 면역증진과 관련된 cytokine인 iNOS, COX-2, IL-1β, IL-6, TNF-α의 발현을 확인하였다. 본 연구를 통해 갈매나무과 분류군들의 부위별 NO 생성능, mRNA 발현 등과 같은 면역 활성에 대한 과학적 근거를 제시할 수 있었고, 이는 면역증진 관련 소재 발굴 및 제품 개발에 기초자료로 활용할 수 있을 것으로 판단된다.