• Mycobiology
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• 제43권4호
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• pp.450-457
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• 2015

Medicinal mushrooms have been used worldwide to treat cancer and modulate the immune system. Over the last several years, there has been increasing interest in isolating bioactive compounds from medicinal mushrooms and evaluating their health beneficial effects. Fomes fomentarius is used in traditional oriental medicine and is known to possess antioxidant, antiinflammatory, antidiabetic, and antitumor effects. In the present study, we isolated fomentariol from Fomes fomentarius and investigated its anti-inflammatory effect in murine macrophages (RAW264.7 cells) stimulated with lipopolysaccharides. Fomentariol inhibited the production of nitric oxide and intracellular reactive oxygen species triggered by lipopolysaccharides. Interestingly, fomentariol differentially regulated cytokine production triggered by lipopolysaccharides. Fomentariol effectively suppressed the production of interleukin-$1{\beta}$ and interleukin-6 but not tumor necrosis factor-${\alpha}$. The inhibitory effect of fomentariol against nitric oxide, interleukin-$1{\beta}$, and interleukin-6 production was possibly mediated by downregulation of the extracellular signal-regulated kinase signaling pathway. Taken together, our results suggest that fomentariol differentially modulated inflammatory responses triggered by lipopolysaccharides in macrophages and is one of the bioactive compounds that mediate the physiological effects of Fomes fomentarius.

• Journal of Applied Biological Chemistry
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• 제64권4호
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• pp.375-382
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• 2021

조록나무는 제주도 및 일본 혼슈 이남, 중국 동남부, 타이완 등에 분포하는 조록나무과의 상록 교목으로, 항산화 및 tyrosinase, elastase의 억제에 효과적인 것으로 알려져 있지만 NO에 대한 억제 효능은 미미한 것으로 보고되었다. 이에 본 연구는 조록나무 잎 추출물(DL)에 biorenovation 생물 전환 기법을 적용하여 항 염증 활성을 증진 시키고자 수행되었다. 이들의 활성은 LPS로 자극된 RAW264.7 염증 모델에서 평가 되었으며 NO, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) 및 전 염증성 사이토카인에 대한 억제 실험이 수행되었다. 그 결과, biorenovation을 적용한 조록나무 잎 추출물(DLB)는 독성이 없는 농도에서 DL대비 향상된 NO와 prostaglandin E2 억제효능을 나타내었으며, 이들의 합성 효소인 iNOS 및 COX-2의 발현에도 유의한 억제 경향을 나타내었다. 또한 대표적인 전 염증성 사이토 카인인 tumor necrosis factor-α, Interleukin 6, Interleukin-1β 에서도 향상된 억제 효능을 확인 하였다. 이러한 결과를 근거로 우리는 biorenovation을 통해 DL의 항염증 효능이 개선될 수 있으며, DLB가 효과적인 천연 항염증 소재로 적용될 수 있음을 제시한다.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.519-526
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• 2023

본 연구는 마우스 대식세포 유래 Raw264.7 세포주에서 황기와 산초 1:1 혼합물(AZM-1:1)의 면역 증진 효능을 탐색하였다. Raw264.7 세포에 100-400 ㎍/mL의 A ZM-1:1 처치는 세포 생존율의 변화 없이 inducible nitric oxide synthase mRNA의 발현 증가와 함께 nitric oxide의 생성을 통계적으로 유의하게 증가시켰다. 더불어 A ZM-1:1은 처치 농도 의존적으로 cyclooxygenase-2 mRNA의 유도와 함께 세포 배양액 중 prostaglandin E₂의 함량을 증가시켰다. 또한, AZM-1:1은 tumor necrosis factor-α, interleukin-1β, interleukin-6 및 monocyte chemoattractant protein-1의 전사를 촉진하였다. Immunoblot 분석을 통하여 AZM-1:1은 mitogen-activated protein kinase의 인산화를 증가시키고, inhibitory-κBα의 인산화를 매개한 분해를 촉진하며, p65의 인산화를 증가시킬 수 있음을 확인하였다. AZM-1:1의 처치는 녹색 형광으로 표지된 대장균 파편의 탐식작용을 촉진하였다. 따라서, 이상의 결과는 A ZM-1:1가 대식세포를 포함한 내재면역을 증진시키는 기능성 식의약 소재가 될 수 있음을 나타낸다.

• 한국미생물·생명공학회지
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• 제50권3호
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• pp.354-360
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• 2022

This research was designed to evaluate the possible anti-inflammatory effects of Carex scabrifolia Steud. extract using RAW264.7 cells. The assessments of these effects were based on cell viability assay, mRNA expression levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNFα), and levels of nitric oxide (NO)/prostaglandin E2 (PGE₂) production. Quantitative real-time polymerase chain reaction showed that treatment with C. scabrifolia Steud. extract decreased the mRNA levels of iNOS, COX2, IL-1α, IL-1β, IL-6, and TNFα. Furthermore, from the production levels of PGE₂/NO, it can be inferred that C. scabrifolia Steud. extract exhibited anti-inflammatory properties. These results suggest that C. scabrifolia Steud. extract contains anti-inflammatory compound(s), and consequently, that it may have applications as a potent cosmeceutical material.

• Advances in Traditional Medicine
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• 제6권1호
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• pp.27-33
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• 2006

The Sasang constitutional medicine classifies the mankind into four constitutional types according to the individual psychological and physical traits. Differences in the Sasang constitutional medicine may be explained by the genetic factors. In order to determine the association of Sasang constitutional classification and interleukin-1 receptor antagonist (IL-1Ra) in genetic susceptibility to ischemic stroke, we classified the four constitutional types in ischemic stroke patients (n = 125) and the healthy control subjects (n = 107), and genotyped for IL-1Ra polymorphism by polymerase chain reaction (PCR) methods. The distribution of the $IL1RN^*1/IL1RN^*2$ genotype in the ischemic stroke patients was significantly different from the healthy controls (OR = 6.09; P =0.0134). And the prevalence of $IL1RN^*1/IL1RN^*2$ genotype was increased in Taeum-in ischemic stroke patients, as compared to Taeum-in healthy controls (OR = 14.71; P = 0.0144). These results suggest that $IL1RN^*1/IL1RN^*2$ genotype in Taeum-in might be associated with the increasing risk for ischemic stroke. Furthermore, this relationship could provide the basis for a new approach in the investigation of the etiology of ischemic stroke.

• Journal of Microbiology and Biotechnology
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• 제28권1호
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• pp.115-121
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• 2018

Upon sensing of microbial infections or endogenous danger signals in macrophages, inflammasome signaling plays a significant role in triggering inflammatory responses via producing interleukin (IL)-$1{\beta}$. Recent studies revealed that active caspase-1, a product of the inflammasome complex, causes maturation of inactive pro-IL-$1{\beta}$ into the active form. However, the underlying mechanism by which this leaderless cytokine is secreted into the extracellular space remains to be elucidated. In this study, we demonstrated that prolonged lipopolysaccharide (LPS) treatment to macrophages could trigger the unexpected maturation and extracellular release of IL-$1{\beta}$ through a nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3)-independent manner. Short-term treatment (less than 6 h) of LPS induced robust production of the IL-$1{\beta}$ precursor form inside cells but did not promote the maturation and secretion of IL-$1{\beta}$ in bone marrow-derived macrophages or peritoneal macrophages. Instead, prolonged LPS treatment (more than 12 h) led to a significant release of matured IL-$1{\beta}$ with no robust indication of caspase-1 activation. Intriguingly, this LPS-triggered secretion of IL-$1{\beta}$ was also observed in NLRP3-deficient macrophages. In addition, this unexpected IL-$1{\beta}$ release was only partially impaired by a caspase-1 and NLRP3 inflammasome inhibitor. Collectively, our results propose that prolonged exposure to LPS is able to drive the maturation and secretion of IL-$1{\beta}$ in an NLRP3 inflammasome-independent manner.

• 대한의생명과학회지
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• 제3권2호
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• pp.139-150
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• 1997

인터루킨-1 (IL-1)을 횐쥐의 기관지로 투여하여 급성 폐손상을 유도하고 폐세척액 내의 단백질 함량 측정과 조직학적, 미세구조적 관찰 및 폐조직 내 $H_2O$$_2$ 분포를 관찰하기 위한 세포화학적 실험을 수행하였다. 또한 노화가 급성 폐손상을 가중시키는 한 요소인지를 검토하였다. IL-1으로 유도된 급성 폐손상은 호중구의 침윤으로 인해 산화적 손상이 가해졌으며, 이로 인해 폐포강 내로 단백질 삼출과 백혈구의 유주가 발생하였다. 하지만 노화에 따른 $H_2O$$_2$분포 양상은 IL-1 투여군 4개월, 20개월간의 차이를 인정할 수 없었다. 따라서 본 연구결과를 통하여 급성호흡곤란 증후군 환자의 폐세척액에서 증가하는 IL-1을 흰쥐의 기관지 내로 투여하여 유도된 급성 폐손상은 호중구의 침윤으로 인한 산화적 손상이 매우 큰 원인으로 작용함을 형태적으로 확인할 수 있었으며, 노화 자체가 급성 폐손상을 가중시키지는 않는 것으로 사료되었다.

• Tuberculosis and Respiratory Diseases
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• 제50권3호
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• pp.300-309
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• 2001

배 경 : 패혈증의 병태생리에는 많은 인자들이 관여를 한다. 이중 ET-1은 혈관수축 및 다장기 부전 등을 초래하고 IL-8은 호중구 매개성 염증반응을 유도하는 역할을 하며, 임상적 지표로서도 유용성이 알려지고 있다. 본 연구는 패혈증 환자에서 ET-1과 IL-8의 혈중농도를 연속적으로 측정하여 변화 양상과 상호 관련성을 평가하고 임상적인 의의를 조사하고자 한다. 방 법 : 패혈증 환자 19예에서 1일, 3일, 7일, 14일에 연속적으로 채혈을 하였고 APACHE III 점수를 측정하였다. 혈청 검체에서 ET-1과 IL-8의 농도를 immunoassay 법으로 측정하였다. 결 과 : 패혈증 환자에서 정상 대조군에 비하여 혈청 ET-1이 유의하게 높았다. 패혈증 환자에 있어서 1일 및 7일 ET-1은 생존군보다 사망군에서 더 높았다. 패혈성 쇼크를 동반한 군에서 1일 ET-1이 높았으며, 혈청 ET-1은 혈청 creatinine과 1일, 7일, 14일에 유의한 상관성이 있었다. 혈청 ET-1과 IL-8 농도는 14일에 서로 유의한 상관성이 나타났다. 결 론 : 패혈증에 있어서 혈청 ET-1은 예후, 패혈성 쇼크, 신부전 등과 관련성이 있었고 IL-8과도 상관성을 보여 임상적인 평가 및 예후 인자로서 유의성을 보였다.

• 대한한의학회지
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• 제27권1호
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• pp.220-228
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• 2006

Objectives : Interleukin-1 (IL-1)${\beta}$ in articular chondrocytes regulates differentiation, apoptosis, and inflammatory responses. It is still controversial, So, we investigated IL- $1{\beta}$ induces chondrocytes dedifferentiation and death. Also, we studied the role of the mitogen-activated protein kinase (MAPK) subtypes on IL-$1{\beta}$-induced dedifferentiation and apoptosis. Methods : To evaluation of dedifferentiation by chemokines of chondrocytes, we assessed such as proteoglycan, collagen, MMP-3 and MMP-13 by RT-PCR analysis. Also, to assess of apoptosis effect by chemokines, we measured annexin V/propidium iodode (PI) and sub G1 cells in chondrocytes by flowcytometric analysis Results : IL-$1{\beta}$ treatment did not affect activation of ERK-1/2, but stimulation of p38 kinase. Inhibition of phospho ERK-1/2 with PD98059 enhanced IL-1b-induced dedifferentiation, and apoptosis up to 13.5%, whereas inhibition of phospho p38 kinase with SB203580 inhibited dedifferentiation, and apoptosis. Conclusions : Our results indicate that SB203580, p38 kinase inhibitor, inhibits IL-$1{\beta}$-induced dedifferentiation, and apoptosis by the inhibition of type II collagen expression and proteoglycan synthesis of rabbit articular chondrocytes.

• Molecules and Cells
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• 제38권10호
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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.