• 생명과학회지
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• 제13권4호
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• pp.441-447
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• 2003

Protein kinase C (PKC)가 interleukin-1 beta (IL-1$\beta$)에 의하여 산화질소(NO) 생성과정에 어떤 역할을 하는지를 검토하기 위하여, 혈관평활근세포에서 PKC 활성제인 phorbol 12-myristate 13-acetate (PMA)로 전처리한 후 IL-1$\beta$에 의하여 야기되는 NO생성을 nitrite ($NO_2$)로 정량하고, RT-PCR method를 이용하여 iNOS 발현에 미치는 영향을 검토하여 다음과 같은 결과를 얻었다. PMA (20, 200 nM)는 IL-1$\beta$에 의한$NO_2$ 생성을 유의하게 증가시켰다. PMA 200 nM, phorbol 12,13-dibutyrate 500 nM로 전처리하여 8, 24시간 노출된 세포에서 IL-1$\beta$에 의한 NO2생성이 현저히 감소되었으나, PKC 비활성제인 4$\alpha$-phorbol-didecanoate 200 nM로 전처리한 경우는 영향을 받지 아니하였다. PMA 농도를 달리하여 24시간 전처리한 경우 IL-1$\beta$에 의한 $NO_2$ 생성의 감소는 PMA의 농도가 20및 200 nM에서 현저하였다. RT-PCR method를 이용하여 iNOS 발현을 검토한바 IL-1$\beta$ 100U/ml에 의한 iNOS발현이 PMA전처리 및 cycloheximide 또는 actinomycin D존재로서 현저히 억제 되었다. 이상의 결과로 미루어 혈관평활근세포에서 PMA 전처리로 야기되는 IL-1$\beta$에 의한 NO 생성의 감소는, PKC 조절저하작용에 의한 iNOS 발현의 억제로 야기되는 것 같다.

• 약학회지
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• 제52권1호
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• pp.62-66
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• 2008

In this study, we examined the inhibitory effects of propenone derivatives, 1,3-diphenyl-propenone (DPhP), 3-phenyl-1-thiophen-2-yl-propenone (PhT2P), 3-phenyl-1-thiophen-3-yl-propenone (PhT3P) and 1-furan-2-yl-3-phenyl-propenone (FPhP), on $TNF-{\alpha}$-induced nuclear factor (NF)-${\kappa}B$ activity and interleukin (IL)-8-induced monocyte adhesion to colon epithelial cells. 1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) that is previously reported as a $NF-{\kappa}B$ inhibitor suppressed $TNF-{\alpha}$-induced monocyte-epithelial cell adhesion in a concentration-dependent manner. The propenone derivatives, DPhP, PhT2P, PhT3P, FPhP, also inhibited $TNF-{\alpha}$-induced $NF-{\kappa}B$ activation in a similar degree to FPP-3. In a DPPH radical scavenging assay, none of the compounds showed DPPH radical scavenging activity, indicating that the inhibitory actions of the propenone derivatives on redox-sensitive $NF-{\kappa}B$ activity is not due to a simple free radical scavenging activity. In addition, the propenone derivatives also suppressed the IL-8-induced monocyte adhesion to colon epithelial cells. Furthermore, the effective concentrations of the propenone derivatives on both $NF-{\kappa}B$ activation as well as IL-8 induced monocyte-epithelial cell adhesion were 1000 times lower than 5-aminosalicylic acid (5-ASA), a clinically used drug for inflammatory bowel disease. These results suggest that the propenone derivatives may be a potential lead having a strong inhibitory activity against inflammatory cytokine-induced epithelial inflammation.

• Tuberculosis and Respiratory Diseases
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• 제45권5호
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• pp.942-952
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• 1998

연구배경: 결핵균(m. tuberculosis) 감염에 대한 숙주의 방어기능에서 세포-매개성 면역반응이 중요하며, 항 결핵반응은 주로 T-림프구와 대식세포에 의하여 매개된다. 결핵균이 대식세포에 탐식되면 특징적인 cytokine이 분비되며 이 cytokine이 잠재적인 면역조절반응과 결핵감염시 여러가지 임상증상을 나타내는데 관여하고, 특히 육아종 형성, 건락성 괴사, 및 지연형 과민반응에 중요한 역할을 한다. 본 연구에서는 활동성 폐결핵환자의 기관지폐포 세척액에서 대식세포에서 분비되는 대표적인 cytokine인 tumor necrosis factor-$\alpha$, interleukin-1$\beta$, interleukin-6와 interleukin-8의 자발 및 LPS 자극 후의 분비를 관찰하고자 하였다. 방 법: 폐결핵 환자 10예와 대조군 5예를 대상으로 기관지폐포 세척술을 시행하여 폐포 대식세포를 분리한 후 RPMI 1640 배양액에 폐포 대식세포가 mi당 $1 {\times}10^6$개가 되도록 희석하여 LPS 0.1 ${\mu}g/ml$, 1 ${\mu}g/ml$, 10 ${\mu}g/ml$을 첨가하거나 첨가하지 않고 $37^{\circ}C$, 5% CO2 하에서 24 시간 및 48시간 배양한 후 상층액에서 TNF-$\alpha$, IL-1$\beta$, IL-6와 IL-8의 분비를 ELISA kit를 이용하여 측정하였다. 결 과: 폐포 대식세포에서 측정한 24 시간 자발적 TNF-$\alpha$의 분비는 이환된 병변 $1149{\pm}805.5$ pg/ml, 대조군 $125{\pm}109.7$ pg/ml, 비병변 $127{\pm}135.6$ pg/ml, IL-6의 분비는 이환된 병변이 $20.6{\pm}16.12$ ng/ml, 대조군 $0.91{\pm}0.58$ ng/ml, 비병변 $1.10{\pm}1.38$ ng/ml로 병변에서 유의하게 현저한 증가를 보였다(p<0.05). 폐포 대식세포에서 LPS 10 ${\mu}g/ml$로 48 시간 동안 자극한 후의 TNF-$\alpha$와 IL-6 분비능은 결핵의 이환된 병변에서 대조군이나 비병변에 1:11하여 증가된 경향을 보였다. IL-1$\beta$와 IL-8의 24시간 자발적 분비능 및 LPS 10 ${\mu}g/ml$로 48시간 동안 자극한 후의 분비능은 결핵 병변의 대식세포에서는 측정되지 못하였으며, 대조군과 비병변에서 얻어진 대식세포에서는 특별한 차이가 없었다. TNF-$\alpha$의 분비는 대부분이 처음 24 시간에 분비되었으나 IL-1$\beta$, IL-6 및 IL-8의 분비는 48시간까지 점차 증가되었다. TNF-$\alpha$, IL-1$\beta$ 및 IL-6는 자발적 분비에 비하여 LPS를 0.1 ${\mu}g/ml$, 1 ${\mu}g/ml$, 10 ${\mu}g/ml$로 증가시킬 수록 분비가 증가되었으나 IL-8은 LPS 1 ${\mu}g/ml$ 시 분비가 고평부를 이루었다. 결핵 비병변에서 얻어진 폐포 대식세포에서 TNF-$\alpha$, IL-1$\beta$ 분비능은 초치료 환자에서 재발환자에 비하여 현저하게 증가되었으나 IL-6와 IL-8의 분비능은 초치료와 재치료 환자에서 큰 차이가 없었다. 결 론: 폐결핵 환자의 폐포 대식세포의 cytokine 분비능은 정상 대조군에 비하여 현저하게 증가되어 있었으나 이는 직접 이환된 부위의 폐포 대식세포에 국한되었다. 또한 폐포 대식세포에서 분비되는 proinflammatory cytokine인 TNF-$\alpha$, IL-1$\beta$가 특히 결핵의 초감염시 균에 대한 방어작용에 중요한 역할을 할 것으로 생각된다.

• The Korean journal of internal medicine
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• 제33권6호
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• pp.1103-1110
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• 2018

Background/Aims: Several epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group. Methods: Patients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin $1{\beta}$ (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor ${\alpha}$ (TNFA) genes of patients with AP were compared to those of normal controls. Results: Between January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN -1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (-118C>T, c47+242C>T, +3954C/T, and -598T>C) and TNFA (-1211T>C, -1043C>A, -1037C>T, -488G>A, and -418G>A). Conclusions: IL1RN -1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.

• 동의생리병리학회지
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• 제20권4호
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• pp.929-935
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• 2006

This study was to investigate the effect of Danchunwhangagam(DCWGG) extract on the production of proinflammatory cytokines in peripheral mononuclear cells (PBMCS) from Cerebral infarction(CI) patients. Methods: We examined that the inhibition rate of tumor necrosis factor $(TNF)-{\alpha},\;interleukin(IL)-1{\alpha},\;IL-1{\beta}$, IL-6, and IL-8 productions in DCWGG pretreatment PBMCs culture supernatant in the lipopolysaccaride(LPS)- or Oesferrioxamine(DFX)-treated cells compared to unstimulated cells. DCWGG inhibited the productions of $TNF-{\alpha},\;IL-1{\alpha},\;IL-1{\beta}$, IL-6, and IL-8 induced by LPS in a dose-dependent manner DCWGG might have regulatory effects on LPS or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.

• Natural Product Sciences
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• 제23권2호
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• pp.92-96
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• 2017

A sesquiterpene was purified from Artemisia iwayomogi methanolic extract during the course of searching anti-inflammatory principle from medicinal plants. A sesquiterpene identified as armefolin inhibited the production of nitric oxide (NO) and attenuated inducible nitric oxide synthase (iNOS) protein level in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Armefolin also down-regulated mRNA expressions of iNOS and pro-inflammatory cytokines, interleukin-$1{\beta}$ and interleukin-6 in LPS-activated macrophages. Moreover, armefolin suppressed the degradation of inhibitory-${\kappa}B{\alpha}$ (I-${\kappa}B{\alpha}$) in LPS-activated macrophages. These data suggest that armefolin from A. iwayomogi can suppress the LPS-induced production of NO and the expression of iNOS gene through inhibiting the degradation of I-${\kappa}B{\alpha}$. Taken together, armefolin from A. iwayomogi might be a candidate as promising anti-inflammatory agent.

• The Korean Journal of Physiology and Pharmacology
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• 제12권2호
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• pp.79-81
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• 2008

The effects of decursinol on various models of sepsis were investigated. Intra-peritoneal pretreatment of mice with various doses of decursinol ($1{\sim}100$ mg/kg) effectively suppressed lethality induced in three mouse models of experimental sepsis, i.e., lipopolysaccharide (LPS)/D-galactosamine (GalN), high-dose LPS (20 mg/kg), and cecal ligation and puncture (CLP). Intra-peritoneal pretreatment of mice with decursinol (50 mg/kg) markedly enhanced the LPS/GalN -induced increase of plasma interleukin-10 (IL-10) levels, without affecting plasma TNF-${\alpha}$, IL-6 and IL-12 levels. These results suggest that decursinol could be effective for prevention or treatment of sepsis.

• Preventive Nutrition and Food Science
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• 제18권1호
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• pp.23-29
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• 2013

This study was designed to investigate the anti-inflammatory effect of oyster shell extract on the production of pro-inflammatory factors [NO, reactive oxygen species (ROS), nuclear factor-kappa B (NF-${\kappa}B$), inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2)] and pro-inflammatory cytokines [Interleukin-$1{\beta}$ (IL-$1{\beta}$), Interleukin-6 (IL-6) and TNF-${\alpha}$] in the lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. Cell viability, as measured by the MTT assay, showed that oyster shell extract had no significant cytotoxicity in Raw 264.7 cells. The treatment with oyster shell extract decreased the generation of intracellular reactive oxygen species dose dependently and increased antioxidant enzyme activities, such as SOD, catalase, GSH-px in LPS-stimulated macrophage cells. Oyster shell extract significantly suppressed the production of NO and also decreased the expressions of iNOS, COX-2 and NF-${\kappa}B$. Additionally, oyster shell extract significantly inhibited the production of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ in LPS-stimulated Raw 264.7 cells. Thus, these results showed that the oyster shell extract had an anti-inflammatory effect on LPS-stimulated Raw 264.7 cells.

• 약학회지
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• 제47권5호
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• pp.311-318
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• 2003

Eurya emarginata (Thunb.) Makino (Theaceae) is distributed in coastal areas of island. The leaves of Eurya are used in the traditional medicine of the coastal areas of jeju island with the aim of diuresis or to treat ulcers. Nevertheless, there are few reports on the biological activity and constituents of E. emarginata. In this study, we investigated the pharmacological activity of the solvent extracts of E. emarginata on the several inflammatory markers (TNF-$\alpha$, IL-1$\beta$, IL-6, NO, iNOS and COX-2). Also we examined the antioxidizing effect of the solvent extracts by determination of DPPH radical-scavenging activity. Among the solvent fractions, EtOAc and BuOH extracts showed potent radical scavenging activity (RC$_{50}$=10.9 and 12.7 respectively). The subtractions of EF 5-4-6-3-2 and BF 1 potentially inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) at the concentration of 100 $\mu\textrm{g}$/mι. Also the fractions inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) and protein expression of iNOS and COX-2 at the concentration of 100 $\mu\textrm{g}$/mι. And then, the inhibition of iNOS was correlated with the decrease of nitrite level. These results suggest that E. emarginata may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines, iNOS and COX-2.2.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.700-718
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• 2003

Fructan, a polysaccharide existing in plants or produced by microorganisms, is a sugar polymer of fructose with $\beta$-2,6 linkages. In this study, we investigated some cosmeceutical properties of Fructan such as moisturizing effect, cell proliferation effect, anti-inflammation effect and cell cytotoxicity. Zymomonas mobilis, a microorganism producing Fructan, was cultured in a medium containing 10％ sucrose and 2％ yeast extract as main components for 24 hours at 37$^{\circ}C$ and pH 7. Fructan was obtained by precipitation from the cultured medium by adding alcohol (alcohol ratio of 1:3) after removing the enzyme by centrifuging. Fructan exhibited almost same moisturizing effect as hyaluronic acid and cell proliferation effect on human fibroblast and keratinocyte as well. Moreover, on cell proliferation test on bio-artificial skin constructed by 3-dimensional(3-D) culture after inducing primary skin inflammation with 0.5％ sodium lauryl sulfate (SLS), the 3-D artificial skin treated with 0.01 mg/ml, 0.05mg/ml of Fructan exhibited higher cell proliferation than the 3-D artificial skin treated with SLS only. On anti-inflammation test on 3-D artificial skin evaluated by measuring secreted quantity of interleukin-1$\alpha$ (IL-1$\alpha$) which is a pre-inflammatory mediator induced by SLS, the quantity of IL-1$\alpha$on the 3-D artificial skin treated with 0.01 mg/ml, 0.05mg/ml of Fructan was less than the one on the 3-D artificial skin treated with SLS only. As a result of these studies, Fructan has anti-inflammation effect against inflammatory reaction by a skin irritant as well as cell proliferation effect in bio-artificial skin. Fructan was also evaluated as a safe material without any toxicity in safety tests using fibroblasts and animals.