Blockade of indoleamine 2,3-dioxygenase protects mice against lipopolysaccharide-induced endotoxin shock.

Jung, In Duk,Lee, Min-Goo,Chang, Jeong Hyun,Lee, Jun Sik,Jeong, Young-Il,Lee, Chang-Min,Park, Won Sun,Han, Jin,Seo, Su-Kil,Lee, Sang Yong,Park, Yeong-Min Williams Wilkins 2009 JOURNAL OF IMMUNOLOGY Vol.182 No.5

<P>Suppression of an excessive systemic inflammatory response is a promising and potent strategy for treating endotoxic sepsis. Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan catabolism, may play a critical role in various inflammatory disorders. In this study, we report a critical role for IDO in the dysregulated immune response associated with endotoxin shock. We found that IDO knockout (IDO(-/-)) mice and 1-methyl-D-tryptophan-treated, endotoxin-shocked mice had decreased levels of the cytokines, TNF-alpha, IL-6, and IL-12, and enhanced levels of IL-10. Blockade of IDO is thought to promote host survival in LPS-induced endotoxin shock, yet little is known about the molecular mechanisms that regulate IDO expression during endotoxin shock. In vitro and in vivo, IDO expression was increased by exogenous IL-12, but decreased by exogenous IL-10 in dendritic cells and splenic dendritic cells. Interestingly, whereas LPS-induced IL-12 levels in serum were higher than those of IL-10, the balance between serum IL-12 and IL-10 following challenge became reversed in IDO(-/-)- or 1-methyl-D-tryptophan-treated mice. Our findings demonstrate that the detrimental immune response to endotoxin shock may occur via IDO modulation. Restoring the IL-12 and IL-10 balance by blocking IDO represents a potential strategy for sepsis treatment.</P>

담배 니코틴에 의한 사람 태아 성상세포에서 종양괴사인자(TNF-α)의 발현 억제작용

손일홍,이성익,양현덕,한선정,석승한,이재규,김재현,박주영,문형인,이성수,Son, Il-Hong,Lee, Sung-Ik,Yang, Hyun-Duk,Han, Sun-Jung,Suk, Seung-Han,Lee, Jai-Kyoo,Kim, Jae-Hyun,Park, Joo-Young,Moon, Hyung-In,Lee, Sung-Soo 대한화학회 2007 대한화학회지 Vol.51 No.3

니코틴은 사람 대식세포에서 interleukin 2 (IL-2)와 종양괴사인자 (tumor necrosis factor-alpha; TNF-α) 가 생성되는 것을 억제하는데, 이러한 억제작용은 cytokine 유전자 발현 중 전사단계에서 전사인자의 활성을 억제함으로써 일어난다. 이러한 니코틴의 면역반응 억제작용은 아프타성궤양 및 궤양성대장염, 알레르기성폐 포염, 건초열 등에서도 보고되고 있다. 만일 중추신경계에서도 위와 같은 니코틴의 면역억제 작용이 일어난 다면 다발성경화증과 같은 면역반응 매개질환의 치료에 새로운 전기가 마련될 수 있을 것이다. 본 연구에서 는 중추신경계의 여러 면역반응 매개질환의 병태생리에 대한 이해를 넓히고자, 이미 알려진 니코틴의 cytokine 생성억제가 사람 중추신경계의 성상세포에서도 일어남을 확인하고 그 억제기전을 밝히고자 하였다. 이를 위 하여 사람 태아 성상세포에 다양한 농도의 니코틴과 IL-1β를 처리한 다음 TNF-α mRNA의 발현 정도와 NF- κB의 활성을 비교, 분석하여 다음과 같은 결과를 얻었다. 1. 사람 태아 성상세포를 0.1-20 μg/ml의 니코틴으로 처리해 본 결과 10 μg/ml 이상의 농도에서 세포독성능이 나타나기 시작하였다. 2. 사람 태아 성상세포에 IL- 1β를 처리하면 2시간만에 TNF-α mRNA가 최대로 발현되었으며 그 이후로는 점진적으로 감소하였다. 3. 사 람 태아 성상세포를 1 및 0.1 μg/ml의 니코틴으로 전처리한 후 IL-1β로 자극한 군에서는 IL-1β 단독 처리군에 비해 TNF-α mRNA의 발현이 감소하는 양상을 보였다. 1 μg/ml의 니코틴을 처리한 경우에는 8시간 이후부터 TNF-α mRNA의 발현이 현저하게 감소하여 12시간에 최대로 감소하였다. 또한 0.1 μg/ml의 니코틴을 처리한 군에서는 24시간에 가장 현저하게 감소하였다. 4. 성상세포에 IL-1β로 처리한 군에서는 강력한 NF-κB의 활성 을 확인할 수 있었으며, 니코틴을 전처리하고 IL-1β 자극한 군에서는 NF-B의 활성이 감소하였다. 결론적으로 일정농도 이상의 니코틴은 세포독성효과를 나타내나 적정한 농도와 시간 경과후 니코틴은 사람 태아 성상세포에서 IL-1β에 의해 유도되는 TNF-α의 발현 감소를 유도하며, 이는 NF-κB의 활성을 감소시킴으로써 나타난다고 생각된다. The Tumor necrosis factor-α, (TNF-α), is involved in the pathogenesis of multiple sclerosis and contributes to the degeneration of oligodendrocytes as well as neurons. Nicotine has been found to have immunosuppressive and inflammation-suppressing effects. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-α at both the mRNA and protein levels in response to interleukin-1 (IL-1) or TNF-α. Nicotine has been shown to influence glial cell functions. To order to explore the role of astrocytes in the production of TNF-α, astrocytes were pretreated with nicotine and are stimulated with IL-1β to determine their effects on TNF-α production. The results are as follows. Cytotoxic effects of nicotine on human fetal astrocytes were noted above 10 μg/ml of nicotine. The effect of IL-1β on TNF-α mRNA expression in primary cultured human fetal astrocytes was maximal at 2 h after IL- 1β(100 pg/ml) treatment. Human fetal astrocytes were pretreated with 0.1, 1, and 10 μg/ml of nicotine and then stimulated with IL-1β (100 pg/ml) for 2 h. The inhibitory effect of nicotine on expressions of TNF-α mRNA in human fetal astrocytes with pretreated 0.1 μg/ml of nicotine is first noted at 8 hr, and the inhibitory effect is maximal at 12 h. The inhibitory effect at 1 μg/ml of nicotine is inhibited maximal at 24 h. Nicotine at 0.1, 1 and 10 μg/ml concentrations significantly inhibits IL-1β-induced NF-κB activation. Collectively, this study indicates that nicotine might inhibit the expression of TNF-α in activated human fetal astrocytes.

Naringin Protects Ovalbumin-induced Asthma through the Down-regulation of MMP-9 Activity and GATA-3 Gene

Chang-Min Lee(이창민),Jeong Hyun Chang(장정현),In Duk Jung(정인덕),Young-Il Jeong(정영일),Noh Kyung Tae(노경태),Hee-ju Park(박희주),Jong-Suk Kim(김종석),Yong Kyoo Shin(신용규),Sung Nam Park(박성남),Yeong-Min Park(박영민) 한국생명과학회 2009 생명과학회지 Vol.19 No.6

Naringin은 레몬, 오렌지에서 발견되는 flavonoid계열에 속하는 물질로 여러 식물과 과일에 다량 함유되어 있다. 항암, 항산화 작용을 하는 것으로 알려져 있는 Naringin을 ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델을 이용하여 치료효과를 알아 보았다. 기관지 폐포 세척액을 회수하여 백혈구의 수적 변화, 제2형 협조T세포(Th2 cell)가 생산하는 IL-4, IL-5의 생산에 미치는 영향과 폐조직에서 matrix metalloproteinase (MMP)-9 활성을 측정하였다. 또한, 최근에 Th1/Th2 전사인자로서 GATA-3가 밝혀졌는데 이번 실험에서 Naringin이 ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델에서 Th1, Th2 싸이토카인과 유전자 발현을 조절할 수 있는가에 대하여 알아보았다 그 결과 기관지 폐포 세척액에서 OVA로 감작하여 천식을 유도한 실험군에서는 호산구의 현저한 증가, Th2 형 싸이토카인(IL-4, IL-5)의 증가가 관찰되었다. 그러나 Naringin을 투여한 그룹에서는 OVA의 감작에 의하여 증가한 각종 염증성 지표들이 감소하거나 정상화 되었다. 또한 OVA에 의하여 증가된 기도저항성이 Naringin 투여에 의하여 감소하였으며 폐조직의 염증성 소견도 뚜렷하게 감소되었다. 이와 같은 연구 결과는 Naringin이 천식의 치료에 유용하게 쓰일 수 있음을 시사해준다. The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.

GATA-3 is a Key Factor for Th1/Th2 Balance Regulation by Myristicin in a Murine Model of Asthma

이규,이창민,정인덕,정영일,천성학,박희주,최일환,안순철,신용규,이상율,염석란,김종석,박영민,Lee, Kyu,Lee, Chang-Min,Jung, In-Duk,Jeong, Young-Il,Chun, Sung-Hak,Park, Hee-Ju,Choi, Il-Whan,Ahn, Soon-Cheol,Shin, Yong-Kyoo,Lee, Sang-Yull,Yeom, S Korean Society of Life Science 2007 생명과학회지 Vol.17 No.8

Myristicin은 육두구에서 발견되는 고농축 정유 중 하나인 물질이다. 하지만 Th1/Th2 면역반응에서 육두구의 항알레르기 효과는 아직 밝혀지지 않았다. 최근에 Th1/Th2 전사인자로서 T-bet, GATA-3가 밝혀졌는데 이번 실험에서 myristicin이 ovalbumin(OVA)으로 유도한 천식(asthma) 생쥐모델에서 Th1,Th2 싸이토카인과 유전자 발현을 조절할 수 있는가에 대하여 알아보았다. 또한 기관지 폐포 세척액을 회수하여 백혈구의 수적 변화, 제2형 협조T세포(Th2 cell)가 생산하는 IL-4, IL-5의 생산에 미치는 영향과 폐조직에서 matrix metalloproteinase (MMP)-9 활성을 측정하였다. 그 결과 기관지 폐포 세척액에서 OVA로 감작하여 천식을 유도한 실험군에서는 호산구의 현저한 증가, Th2 형 싸이토카인(IL-4, IL-5)의 증가가 관찰되었다. 그러나 myristicin을 투여한 그룹에서는 OVA의 감작에 의하여 증가한 각종 염증성 지표들이 감소하거나 정상화 되었다. 또한 OVA에 의하여 증가된 기도저항성이 myristicin 투여에 의하여 감소하였으며 폐조직의 염증성 소견도 뚜렷하게 감소되었다. 이와 같은 연구 결과는 myristicin이 천식의 치료에 유용하게 쓰일 수 있음을 시사해준다. Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.

Inflammatory Endotypes of Chronic Rhinosinusitis in the Korean Population: Distinct Expression of Type 3 Inflammation

Min Jin-Young,Kim Jin Youp,성충만,Kim Seon Tae,조현진,문수진,Cho Sung-Woo,Hong Sang Duk,Ryu Gwanghui,Cho Kyoung Rai,Kim Young Hyo,Park Soo-Kyoung,Kim Dong-Kyu,Lee Dong Hoon,Heo Sung Jae,Lee Ki-Il,Kim Su Jin,Le 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.4

Purpose: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters. Methods: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1β, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-β1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster. Results: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype. Conclusions: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS.

Nicotine Suppresses TNF-${\alpha}$ Expression in Human Fetal Astrocyte through the Modulation of Nuclear Factor-${\kappa}B$ Activation

Son, Il-Hong,Park, Yong-Hoon,Yang, Hyun-Duk,Lee, Sung-Ik,Han, Sun-Jung,Lee, Jai-Kyoo,Ha, Dae-Ho,Kang, Hyung-Won,Park, Joo-Young,Lee, Sung-Soo The Korean Society of Toxicogenomics and Toxicopro 2008 Molecular & cellular toxicology Vol.4 No.2

Parkinson's disease (PD) progresses severely by a gradual loss of dopaminergic neurons in the substantia nigra (SN). Epidemiological studies showed that the incidences of PD were reduced by smoking of which the major component, nicotine might be neuroprotective. But the function of nicotine, which might suppress the incidences of PD, is still unknown. Fortunately, recently it was reported that a glial reaction and inflammatory processes might participate in a selective loss of dopaminergic neurons in the SN. The levels of tumour necrosis factor (TNF)-${\alpha}$ synthesised by astrocytes and microglia are elevated in striatum and cerebrospinal fluid (CSF) in PD. TNF-${\alpha}$ kills the cultured dopaminergic neurons through the apoptosis mechanism. TNF-${\alpha}$ release from glial cells may mediate progression of nigral degeneration in PD. Nicotine pretreatment considerably decreases microglial activation with significant reduction of TNF-${\alpha}$ mRNA expression and TNF-${\alpha}$ release induced by lipopholysaccharide (LPS) stimulation. Thus, this study was intended to explore the role of nicotine pretreatment to inhibit the expressions of TNF-${\alpha}$ mRNA in human fetal astrocytes (HFA) stimulated with IL-$1{\beta}$. The results are as follows: HFA were pretreated with 0.1, 1, and $10{\mu}g/mL$ of nicotine and then stimulated with IL-$1{\beta}$ (100 pg/mL) for 2h. The inhibitory effect of nicotine on expressions of TNF-${\alpha}$ mRNA in HFA with pretreated $0.1{\mu}g/mL$ of nicotine was first noted at 8hr, and the inhibitory effect was maximal at 12 h. The inhibitory effect at $1{\mu}g/mL$ of nicotine was inhibited maximal at 24 h. Cytotoxic effects of nicotine were noted above $10{\mu}g/mL$ of nicotine. Moreover, Nicotine at 0.1, 1 and $10{\mu}g/mL$concentrations significantly inhibited IL-$1{\beta}$-induced TF-${\kappa}B$ activation. Collectively, these results indicate that in activated HFA, nicotine may inhibit the expression of TNF-${\alpha}$ mRNA through the pathway which suppresses the NF-${\kappa}B$ activation. This study suggests that nicotine might be neuroprotective to dopaminergic neurons in the SN and reduce the incidences of PD.

Slit 이동장치 제작 및 거리변화법에 의한 감도측정과의 비교 검토

박종삼,박명환,권덕문,이준일 대구보건대학 1995 대구보건대학 論文集 Vol.15 No.-

The slit moving apparatus which determine the advantage of opt-sentive material in sensitometry was produced and was compared to the distance scale method which has low variation in accuracy and in reproduction, and the results showed that the unique value agree. The slit moving apparatus is expect to reduce space which needs widely for sensitometry in distance scale method and improve convince to user.

실관막에 의한 화학슬러지 중 철(Fe) 회수에 관한 연구

박동원,황덕기,김영일 동아대학교 환경문제연구소 1992 硏究報告 Vol.15 No.2

The metal extractions in microporous hollow fiber modules cut down the cost of energy and gain the enlargement of separation efficiency because of their large surface area per unit volumn. This study examines Fe(Ⅲ) separation in wastewater and the optimum separation condition from values of overall mass transfer coefficient, with hollow fiber membrane module, using tri-n-octylamine as extractant. The experimental results are as follows. 1. The separation rate was maximum at pH 2 and as pH in Fe(Ⅲ) solution grew, overall mass transfer coefficient was decreased. 2. As the flow rate of feed solution in the hollow fiber module increased, overall mass transfer coefficient was increased. 3. In the transfer resistance in the hollow fibers, the mass transfer resistance which follows solute diffusion in the hollow fibers dominated overall mass transfer resistance.

K-와 Na-silicate로부터 고품질 silica gel의 합성 : 조제산도 및 숙성 기간의 영향

박종삼,권덕문,이준일 대구보건대학 2001 대구보건대학 論文集 Vol.21 No.-

Inorganic silica precursors like sodium (Na-) and potassium (K-) silicates are much cheaper than organic silica precursors like tetraalkoxysilanes. In order to enhance the quality of silica gels synthesized from soduim and potassium silicates, the effect of aging time, pH and SiO₂ concentration on the properties of silica gels were examined in this study. The presence of different cations in initial sol made slight differences in resulted silica gels. Na-silicate led to more microporous gels than K-silicate under similar preparation conditions. Although similar aging effects were observed in both silicates, more decrease in micropore volume was noticed in Na-silicate with aging time than in K-silicate. Na silicate resulted in the highest surface area at the initial pH of 4.0, while the initial pH of 3.5 led to the highest surface area in K-silicate. Surface areas of resulted gels ranged over 700 ㎡/g, of which values were much higher than usual silica gels obtained from inorganic precursors.

診斷用 X線 發生裝置의 整流方式에 따른 性能 比較

朴明煥,權德文,朴鍾三,李準逸 대구보건대학 1995 대구보건대학 論文集 Vol.15 No.-

Inverter generators are now on the way for further development to eliminate single phase generators and three phase generators. We compared inverter type X-ray apparatus with conventional single phase 2 peak and three phase 12 peak apparatus in the following aspects X-ray output to tube voltage, linearity of X-ray output to mA and exposure time, transmission dose in various thickness of aluminium absorber with different kVp. The output, linearity of inverter type and three phase 12 peak showed increase as compared against of single phase 2 peak X-ray generator. The transmitted doses of inverter type and three phase 12 peak X-ray generators were more increased than single phase 2 peak X-ray generator.