• 약학회지
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• 제47권3호
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• pp.180-183
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• 2003

Crystal structure of TRAF6 in complex with TRAF6-binding sites from CD40 was previously determined. The structure revealed a distinct TRAF6-binding groove of CD40, the key structural determinant of interaction. The structural information leads to a proposed TRAF6-binding motif. This allows the identification of TRAF6-binding sequences in the hIRAK protein, whose functional requirement in IL-1/Toll-like receptor superfamilies-mediated signal transduction is further demonstrated using site-directed mutagenesis. The mutational effects of hIRAK on the down-stream NF-kB signaling shows the importance of the TRAF6 interface for signaling by IL-1/Toll-like receptor superfamilies.

• 대한본초학회지
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• 제31권4호
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• pp.1-10
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• 2016

Objectives: In Korean medicine, Curculiginis Rhizoma was treated for arthritis in remedy. But efficacy of Curculiginis Rhizoma on collagen induced arthritis was not revealed.Methods: Anti inflammatory effect of Curculiginis Rhizoma was researched in vitro with RAW264.7 cell and cell toxicity, levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-12) and PGE2 were analyzed by ELISA assay. Inflammatory protein were analyzed by western blotting assay (JNK, ERK, COX-2, TNF-α and IL-1β). In vivo, collagen induced arthritis mice model was used to evaluate anti-inflammation effect through arthritis index, immune cell number and cytokine levels (TNF-α, IL-6 and IL-1β) in serum.Results: ECR(Extract of Curculiginis Rhizoma) has not shown cell toxicity in 200 ㎍/㎖ on RAW264.7 cell. ECR suppressed releases of NO, TNF-α, IL-1β, IL-6, IL-12 and PGE2 on RAW264.7 cell treated with lipopolysacharide (1 ㎍/㎖). And ECR inhibited regulation of TNF-α, IL-1β and IL-6 mRNA, reduced protein release of JNK, ERK, iNOS, COX-2, IL-1β and TNF-α. AI of group treated with ECR 200 ㎎/㎏ and 100 ㎎/㎏ were significantly decreased compared to vihicle arthritis mice, the number of immune cell in foot joint was increased on control mice but those of group treated with ECR 200 ㎎/㎏ and 100 ㎎/㎏ were significantly reduced. This results correspond with contens of cytokines (TNF-α, IL-1β and IL-6) in serum.Conclusions: Curculiginis Rhizoma has anti-inflammation effect on RAW264.7 cell in vitro and collagen induced arthritis in vivo. So it is necessary to research more mechanism for cascade imfact.

• Clinical and Experimental Pediatrics
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• 제49권9호
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• pp.977-982
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• 2006

목 적 : M. pneumoniae는 기도 점막의 상피세포에서 증식하면서 호흡기 질환을 일으키며 기관지 천식의 발생이나 악화와 관계된다고 알려져 있다. IL-6은 급성 염증을 유도하는 사이토카인으로 B 세포의 분화에 관여하며 Th2 염증반응을 촉진시키며, IL-8은 기도에서 염증부위로의 세포이동을 매개하는 케모카인으로 알레르기 염증 반응에 밀접한 관련을 가진다. 기도 상피세포에서 생성되는 NO는 기도 염증과 기도과민성의 조절에 중요하다. VEGF는 천식에서 기도개형에 주된 역할을 담당한다. 본 연구에서는 기관지 상피세포에 M. pneumoniae를 감염시켰을 때 IL-6, IL-8, NO 및 VEGF의 발현을 살펴보았다. 방 법 : M. pneumoniae를 기관지 상피 세포주인 A549 세포에 감염시킨 후 여러 시간 간격으로 배양하여 세포와 배양 상층액을 수거하였다. 면역 형광 염색과 M. pneumoniae 16S ribosomal RNA gene의 oligonucleotide primers를 이용한 중합효소 연쇄반응을 시행하여 감염을 확인하였다. IL-6, IL-8, VEGF 단백질 생성은 ELISA kit를 이용하여 정량하였고, NO는 Griess 반응을 이용하여 측정하였다. 역전사 중합효소 연쇄반응을 이용하여 IL-6, IL-8, VEGF의 mRNA 발현을 관찰하였다. 결 과 : 기관지 상피세포에 M. pneumoniae를 감염시킨 후 시간이 지남에 따라 IL-6, IL-8, NO, VEGF의 생성이 증가하였고, IL-6, IL-8, VEGF mRNA 발현이 증가됨을 관찰하였다. 결 론 : M. pneumoniae 감염은 IL-6, IL-8, NO, VEGF 등의 매개물질의 발현을 증가시켜 기관지 천식의 알레르기 염증반응에 관여할 것으로 사료된다.

• 대한본초학회지
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• 제28권2호
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• pp.93-101
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• 2013

Objects : Baicalein is a major bioactive flavonoid component of Scutellaria baicalensis Georgi that shows a wide range of biological activities, including neuroprotections and anti-inflammatory actions. Hence it is a potential therapeutic material for the treatment of neuroinflammation. In this study, we investigated the modulatory effect of baicalein on neuroinflammation. Method : Pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 mRNA), COX-2 mRNA expression and microglial activation in the brain tissue is induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Baicalein was treated orally with 10, 20, and 30 mg/kg 1 hour prior to the LPS (3 mg/kg, i.p.) injection. TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction(PCR) method. Iba1 expression in the brain was measured by western blotting method. Microglia was observed with immunohistochemistry. Results : Baicalein 30 mg/kg significantly attenuated the expression of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA in the brain tissue. Baicalein 20 mg/kg significantly attenuated the expression of IL-6 mRNA in the brain tissue. Baicalein 30 mg/kg significantly attenuated the expression of Iba1 protein expression in the brain tissue. Baicalein 30 mg/kg significantly decreased the number and cell size of microglia in the cerebral cortex and hypothalamic region and the area percentage of Iba1-expressed microglia in the hippocampus. Conclusion : These results demonstrated that baicalein attenuates LPS induced neuroinflammation in the mice via reduction of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6), COX-2 mRNA expression and microglial activation.

• Preventive Nutrition and Food Science
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• 제20권2호
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• pp.83-87
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• 2015

Omega-3, a polyunsaturated fatty acid, is an essential fatty acid necessary for human health, and it protects against cardiovascular disease, inflammation, autoimmune diseases, and cancer. In the present study, we investigated the effects of omega-3-rich harp seal oil (HSO) on the production of nitric oxide (NO) and cytokines, such as tumor necrosis factor (TNF)-${\alpha}$, interleukin-(IL)-$1{\beta}$, IL-6, and IL-12/IL-23 (p40) in peritoneal macrophages of mice. The culture supernatants of murine macrophages exposed to lipopolysaccharide (LPS), HSO, or HSO+LPS were harvested to assay IL-$1{\beta}$, TNF-${\alpha}$, IL-6, and IL-12/IL-23 (p40) cytokines and NO. TNF-${\alpha}$, IL-$1{\beta}$, and IL-12/IL-23 (p40) levels, except IL-6, were lower in the culture supernatants of mouse peritoneal macrophages exposed to LPS plus HSO than those of the groups exposed to LPS alone. These observations demonstrate that omega-3-rich harp seal oil downregulates the production of the pro-inflammatory cytokines such as IL-$1{\beta}$, TNF-${\alpha}$, and IL-12/IL-23 (p40). These results suggest that HSO could be potentially used as a preventive agent or as an adjunct in anti-inflammatory therapy, if more research results were accumulated.

• 한방재활의학과학회지
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• 제23권2호
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• pp.73-83
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• 2013

Objectives : This study was performed to investigate the effects of Foeniculum Vulgare(FV) extract on the anti-inflammatory of lipopolysaccharide(LPS) exposed rats. Methods : We divided LPS exposed Sprague-Dawley rats into 4 groups. They were control group, feed with 100 mg/kg, 200 mg/kg, 300 mg/kg FV groups. They were administered for 6 weeks. We measured the concentration of plasma interleukin-1${\beta}$(IL-1${\beta}$), plasma interleukin-6(IL-6), plasma tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), plasma interleukin-10(IL-10), the concentration of liver IL-1${\beta}$, IL-6, TNF-${\alpha}$ and IL-10. Results : 1. Plasma IL-1${\beta}$, plasma IL-6 and plasma TNF-${\alpha}$ concentration increased rapidly at 2hours after LPS injection and maintained high levels at 5hours after LPS injection. The concentration of these cytokines in the FV extract groups showed lower values than control group(P<0.05). 2. The concentration of Plasma IL-10 in FV extract groups showed higher values than control group at all times(P<0.05). 3. The concentration of liver IL-1${\beta}$ and IL-6 in FV extract groups showed lower values than control group(P<0.05). The concentration of liver TNF-${\alpha}$ in FV extract groups showed a tendency to decrease and that of liver IL-10 in FV extract groups showed a tendency to increase; however, these values showed no significantly different. Conclusions : In inflammatory response by LPS derivation, the FV gives positive effect.

• 한국자원식물학회지
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• 제27권6호
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• pp.707-713
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• 2014

This study examined the inflammatory reaction effects of Allium victorialis var. platyphyllum in vivo at the time of a lipopolysaccharide (LPS) shock in rats, and in vitro in cultured Raw 264.7 cells, with the aim of facilitating the development of a new anti-inflammatory medicine. Plasma concentrations of interleukin (IL)-$1{\beta}$, IL-6, tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$), and IL-10 in rats peaked 5 h after LPS treatment in all experimental groups, with those of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ being significantly lower in all animals treated with A. victorialis than in the control group at that time point. Conversely, the plasma concentration of IL-10 was higher in the rats treated with 300 mg/kg A. victorialis extract than in the control group at both 2 and 5 h after LPS treatment. Concentrations of IL-$1{\beta}$ and IL-6 in the liver of rats treated with A. victorialis extract were significantly lower than those of the saline-treated control group. However, the liver concentrations of TNF-${\alpha}$ and IL-10 did not vary significantly between the four animal groups. Similarly, concentrations of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ obtained from cultured Raw 264.7 macrophages were lower in all of the A.-victorialis-extract-treated groups than in the control group. Although the concentration of IL-10 in the A.-victorialis-extract-treated groups tended to be greater than in the control group, the differences between groups were not statistically significant. Together the findings of this study suggest that A. victorialis var. platyphyllum contains functional substances that are involved in inflammatory reactions.

• Journal of Chest Surgery
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• 제32권11호
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• pp.971-977
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• 1999

Background: Immunologic and inflammatory responses of cardiopulmonary bypass(CPB) influence postoperative mortality and morbidity with multiple organ injury. It has been reported that ischemia/reperfusion induced-myocardial injury during CPB is causative of release of inflammatory cytokines such as interleukin-6(IL-6) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). The purpose of this study was to detect the time course of the activated cytokine and troponin-T(TnT), and to examine the correlation between such parameters during CPB. Material and Method: The serial samples were collected from arterial blood via radial arterial catheter in 23 patients who are underwent open heart surgery (OHS) with CPB, the IL-6, TNF-$\alpha$ and TnT were checked. Result: \circled1 IL-6, TNF$\alpha$- and TnT concentration increased significantly during CPB with a peaking level of CPB-off (p 0.05). \circled2 IL-6 had highly positive correlation with aortic cross clamping time and total bypass time(r=0.80, 0.78; p 0.05, respectively). \circled3 There was no correlation among IL-6, TNF-$\alpha$ and TnT. Conclusion: In conclusion, these data showed that elevated production of serum IL-6 during CPB was attributable to ischemia/reperfusion induced-myocardial damage. IL-6 will become a new and sensitive biological marker in assessment of myocardial damage during OHS with CPB. However, further studies will be needed to apply IL-6 in more patient population.

• Biomolecules & Therapeutics
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• 제23권1호
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• pp.84-89
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• 2015

We investigated the question of whether 7-oxygenated cholesterol derivatives could affect inflammatory and/or immune responses in atherosclerosis by examining their effects on expression of IL-23 in monocytic cells. $7{\alpha}$-Hydroxycholesterol ($7{\alpha}OHChol$) induced transcription of the TLR6 gene and elevated the level of cell surface TLR6 protein in THP-1 monocytic cells. Addition of an agonist of TLR6, FSL-1, to TLR6-expressing cells by treatment with $7{\alpha}OHChol$ resulted in enhanced production of IL-23 and transcription of genes encoding the IL-23 subunit ${\alpha}$ (p19) and the IL-12 subunit ${\beta}$ (p40). However, treatment with 7-ketocholesterol (7K) and $7{\beta}$-hydroxycholesterol ($7{\beta}OHChol$) did not affect TLR6 expression, and addition of FSL-1 to cells treated with either 7K or $7{\beta}OHChol$ did not influence transcription of the genes. Pharmacological inhibition of ERK, Akt, or PI3K resulted in attenuated transcription of TLR6 induced by $7{\alpha}OHChol$ as well as secretion of IL-23 enhanced by $7{\alpha}OHChol$ plus FSL-1. Inhibition of p38 MAPK or JNK resulted in attenuated secretion of IL-23. These results indicate that a certain type of 7-oxygenated cholesterol like $7{\alpha}OHChol$ can elicit TLR6-mediated expression of IL-23 by monocytic cells via PI3K/Akt and MAPKs pathways.

• Clinical and Experimental Reproductive Medicine
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• 제33권1호
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• pp.45-52
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• 2006

목 적: 자궁내막증과 이로 인한 불임의 원인인 면역학적 인자 중 세포-매개성 면역계의 변화 양상을 규명하기 위하여 자궁내막증 환자와 자궁내막중이 없는 환자의 복강 액을 채취하여 면역 세포의 분포양상을 비교 분석하고자 IL-6와 TNF-${\alpha}$를 측정하였다. 연구방법: 자궁내막증으로 육안적 또는 조직검사로 확진된 환자 또는 불임검사를 위해 진단적 복강경을 시행한 34명을 연구군으로 등록하였으며 본 연구 이전에 자궁내막증과 관련된 어떠한 치료도 받은 적이 없거나 복강경 시술이나 개복수술과정에서 자궁내막증 소견과 증상이 없는 환자 37명을 대조군으로 하였다. 두 군의 복강 액을 추출한 다음 30분 이내에 $400g{\times}10$분 동안 원심분리 후 상층액만 검사용기에 모아 밀봉한 후 $-70^{\circ}C$ 냉동실에 보관하여 IL-6와 TNF-${\alpha}$의 농도를 "sandwich" enzyme-linked immunosorbent assays (ELISA: R & D Systems, Minnepolis, MN)로 측정하였다. 결 과: 1. 복강 액의 IL-6의 농도는 자궁내막증으로 확진된 연구군에서는 $38.9{\pm}19.7pg/ml$으로 대조군의 $22.4{\pm}10.2pg/ml$보다 유의하게 증가하였고 (p=0.02), TNF-${\alpha}$의 농도도 자궁내막증이 있는 여성에서 $20.6{\pm}8.6pg/ml$로 대조군의 $6.2{\pm}3.5pg/ml$보다 유의하게 증가하였다 (p=0.01). 2. 자궁내막증여성의 생리주기별 농도에서 IL-6은 증식기보다 분비기에 유의하게 증가한 반면 (p=0.01), TNF-${\alpha}$는 차이가 없었다 (p>0.05). 3. IL-6은 가임여성보다 불임여성에서 유의하게 증가하였고 (p=0.03), TNF-${\alpha}$는 두 군 간에 유의한 차이는 없었다 (p>0.05). 4. IL-6과 TNF-${\alpha}$ 모두 대조군과 자궁내막증 병기 I과 II는 통계학적인 유의성은 없었으나 병기 III과 IV는 유의하게 증가하였다 (p<0.05). 결 론: 자궁내막증인 환자의 복강 액에서 IL-6와 TNF-${\alpha}$가 증가하여 자궁내막증의 생성과 유지, 증상발현에 관여하며 불임의 유발 요인으로 여겨지나 향후 많은 환자를 대상으로 한 연구와 자궁내막증과 각종 cytokine과의 상호 연관관계에 대한 연구가 더 많이 필요하리라 사료된다.