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.

Sequential evolution of IL-17 responses in the early period of allograft rejection

Sang Il Min,하종원,박정규,Jae Kyung Won,Yang Jin Park,민승기,김상준 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.10

In addition to CD4+CD25+Foxp3+ regulatory T (Treg) cells which protect against autoimmune tissue injury, IL-17-producing CD4+ T (Th17) cells have been recently described and shown to play a crucial role in autoimmune injury. It appears that there is a reciprocal developmental pathway between Th17 and Treg cells. Although IL-17 is known to be associated with allograft rejection, the cellular source of IL-17 and the nature of Th17 in the context of allograft rejection remain unknown. In the current study, the dynamics of Treg and IL-17-producing cells after syngeneic and allogeneic transplantation were examined using a wild-type murine cardiac transplantation model. Ly6G+ cells were found to produce IL-17 during the early postoperative period and CD8+ as well as CD4+ T cells were also found to produce IL-17 during alloimmune response. Graft-infiltrating Ly6G+, CD4+, and even CD8+ cells were found to express IL-17 highly compared to those in spleen. Although the frequencies of Th17 and Treg were found to gradually increase in both syngeneic and allogeneic recipients, Th17/Treg ratios were significantly higher in recipients with allograft rejection than in syngeneic recipients. In conclusion, IL-17 is produced by neutrophils during the early postoperative period and subsequently by Th17 and CD8+ T cells during allograft rejection. Th17/Treg imbalance is associated with the development of allograft rejection. This study would provide basic information on Th17 biology for future investigation in the field of transplantation.

Intracellular IL-4, IL-10, and IFN-gamma levels of leukemic cells and bone marrow T cells in acute leukemia.

Park, Hun Hee,Kim, Myungshin,Lee, Bong-Hee,Lim, Jihyang,Kim, Yonggoo,Lee, Eun Jung,Min, Woo Sung,Kang, Chang Suk,Kim, Won Il,Shim, Sang In,Han, Kyungja Institute for Clinical Science] 2006 Annals of clinical and laboratory science Vol.36 No.1

<P>The quantitative levels of intracellular cytokines IL-4, IL-10, and IFN-gamma (ie, the number of bound PE-conjugated antibody molecules/cell) of leukemic cells and bone marrow T cells (bmT cells) of acute leukemia patients were analyzed by flow cytometry. One hundred, thirty-one (95 AML, 25 ALL, 11 ABL) patients were studied. The leukemic cell IL-4 level was highest in the monocytic AML group (1735 +/- 1056) and lowest in the dysplastic AML group (960 +/- 545). The IFN-gamma level was highest in the acute promyelocytic leukemia (APL) group (495 +/- 159), and lowest in the ALL group (252 +/- 119). The IL-10 level was not significantly different among the diagnosis groups. In bmT cells, the IL-10 level was highest in the dysplastic AML group (972 +/- 1049) and lowest in the APL group (397 +/- 352). The leukemic cell cytokine levels were lowest and bmT cell cytokine levels were highest in the dysplastic AML group. There were no significant correlations of these cytokine levels with 2-yr survival rate, complete remission (CR) rate, or relapse rate. The cytokine levels of bmT cells at the time of CR became normal and were not different among the diagnosis groups. In summary, leukemic cell and bmT cell cytoplasmic expression profiles of IL-4, IL-10, and IFN-gamma are characteristic for each diagnostic group of acute leukemia patients and the profiles of bmT cells are normal at the time of CR.</P>

금은화, 연교, 포공영 혼합물의 항염증 작용에 관한 연구

최강민 ( Kang Min Choi ),전주현 ( Ju Hyun Jeon ),김은석 ( Eun Seok Kim ),성기정 ( Ki Jung Sung ),김영일 ( Young Il Kim ) 대전대학교 한의학연구소 2021 혜화의학회지 Vol.30 No.1

Objective : The purpose of this study is to investigate the inflammatory-control effects of Cheonghyeol-antidote complex(Lonicera japonica Thunberg, Forsythia viridissima Lindley, and Taraxacum platycarpum H. Dahlstedt complex, CHA) in LPS-induced RAW264.7 cell and mouse inflammation models. Method : For in vitro and in vivo experiment, Indicators such as cell viability, mRNA expression level(iNOS, IL-6, IL-1β, COX-2, TNF-a), Inflammatory factor production(NO, IL-6, IL-1β, TNF-a), and protein phosphorylation level(ERK, JNK, p38) were analyzed. For in vivo experiment, Indicators such as mRNA expression level(iNOS, IL-6, IL-1β, COX-2, TNF-a), Inflammatory factor production(IL-6, IL-1β, TNF-a), protein phosphorylation level(ERK, JNK, p38) and immune cell(white blood cell, lymphocyte) were analyzed. Results : 1. In vitro experiment In cell viability of CHA, CHA showed cell viability below 90% at concentrations of 400 μg / ml or more. In mRNA expression level, IL-6 and IL-1β showed a significant decrease at all concentrations except 25 μg / ml concentration, and iNOS, COX-2, and TNF-a showed a significant decrease at all concentrations of CHA compared to the control group. In inflammatory factor production, NO and TNF-a showed a significant decrease at all concentrations except 25 μg / ml concentration of CHA, and IL-1β showed a significant decrease at 100, 200 μg / ml concentration of CHA compared to the control group. IL-6 showed a significant decrease at all concentration of CHA compared to the control group. In protein phosphorylation level, ERK and p38 showed a significant decrease at all concentrations except 25 μg / ml concentration of CHA and JNK showed a significant decrease at all concentrations of CHA compared to control group. 2. In vivo experiment In mRNA expression level, iNOS, COX-2 and TNF-a showed a significant decrease in all administration groups of CHA compared to the control group. In Inflammatory factor production, IL-6, IL-1β and TNF-a showed a significant decrease in all the administration groups of CHA. In protein phosphorylation level, ERK, JNK, and p38 showed a significant decrease in all the administration groups of CHA. In the immune cells, leukocytes and lymphocytes showed a significant decrease in all the administration groups of CHA. Conclusions : This study shows that CHA has antioxidant and inflammatory-control effects on LPS-induced RAW264.7 cells. It is hoped that further research will be conducted on the individual mechanisms of Lonicera japonica Thunberg, Forsythia viridissima Lindley, and Taraxacum platycarpum H. Dahlstedt.

OMC-2010 추출물이 마우스의 비장세포 cytokine 생성에 미치는 영향

배기상 ( Gi Sang Bae ),박경철 ( Kyoung Chel Park ),최선복 ( Sun Bok Choi ),조일주 ( Il Joo Jo ),서상완 ( Sang Wan Seo ),김종진 ( Jong Jin Kim ),신용국 ( Yong Kook Shin ),김민선 ( Min Sun Kim ),박규환 ( Kyu Hwan Park ),김현식 ( Hyu 대한본초학회 2012 大韓本草學會誌 Vol.27 No.5

Objective : This study was performed to estimate the effects of OMC-2010 extract on cytokine production in mouse spleen cells. Methods : Mouse spleen cells were pre-treated with ethanol and water extract of OMC-2010 for 1 h, then stimulated with lipopolysaccharide (LPS, 1 μg/ml) for 48 h. Then the cells were harvested for real-time reverse transcription polymerase chain reaction to detect cytokines. Results : OMC-2010 ethanol extract significantly inhibited the LPS-induced interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-5 mRNA expressions, but not shown such changes in IL-6, IL-4, IL-13. OMC-2010 water extract significantly inhibited the LPS-induced TNF-alpha, and IL-5 mRNA expressions, but not shown such changes in IL-1beta, IL-6, IL-4, IL-13. Conclusions : Theses results could suggest that both ethanol and water OMC-2010 extract could inhibit the TNF-alpha and IL-5 mRNA expression.

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>

사상체질론의 정신의학적 타당성에 대한 연구

민성길,김동기,박진균,전세일 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.3

연구목적 : 건간한 의대상 312명과 신경증적 장애를 가진 환자 288명을 대상으로 하였다. 사상체질의 구별은 노정우 및 김달래 두 전문가에 의한 판정, 그리고 경희의대 사상체질 설문지(QSCC Ⅱ)에 의한 판정 등 3가지 방법에 의하였다. 연구 대상에게 정신과적 증상척도(SCL-90), 체질특성척도 및 성격척도를 사용하여 자가 평가하게 하였다. 각종 척도들의 타당도와 신뢰도는 입증되었다. 이 척도들을 통계적으로 분석하고 고전적 설명과 어느 정도 일치하는 지를 검토하였다. 연구결과 : 1) 3가지 분류방법간에 차이가 컸었다. 그 중 전문가의 직접적 면담에 의한 감별보다 QSCCⅡ 설문지형이 비교적 감별력이 컸다. 3) QSCCⅡ가 감별력이 비교적 크다고 하더라도 그 결과가 소음군의 대인공포-강박증, 불면-식용상실, 무력-예민-소화기-한기-피부증후군 그리고 정력부족등 신경증적 증상과 소극-비사교적, 내향형 성격 및 이성적 성격특징 등 몇가지 특징을 감별하는 데에만 비교적 유의하였고, 태음군의 특정인 독특한 신념, 온기, 활달-사교적 성격에 대해서는 부분적으로 그 특징을 감별하였다. 또한 소양군의 활달-사교형 성격과 감정형 성격의 특징 등은 극히 부분적으로 감별하였다. 결 론 : 이러한 결과는 현존하는 사상체질 구분방법에 일치점이 결여되어 있다는 것, 각종척도를 사용한 결과는 사상체질에 관한 고전적 설명을 부분적으로만 입증하고 있다는 것, 따라서 사상체질구분에 대한 향후보다 객관적인 연구가 필요하다는 것을 시사한다. Object : This study is to examine the validity of constitutional classification of Sa-sang medical theory. This theory classifies the human constitution to 4 types according to classical oriental philosophy on yin and yang. Subjects and Method : Subjects were 312 medical students and 288 neurotic patients with diagnosis of neurotic, stress related and somatoform disorders and minor depressive episodes according to ICD-10. Medical students were classified to 4 Sa-sang Constitution Classification(QSCCⅡ). For assessmnent of symptoms and signs, Korean version of SCL-90, a constitution scale and personality scale which were designed for this study were used. These instruments were found to be reliable and valid through statistical analysis. Subjects were asked to rate these scales. The data were analysed with factor analysis and factor scores were compared among 4 Sa-sang constitutions by ANOVA and t-test. The data from patient group were analysed with factor analysis and the results were compared with the Sa-sang medical theory. Results : Results of classification by 3 ways were inconsistent showing a significant difference among them. Among them, QSCCⅡ was most reliable. In QSCC Ⅱ, only the factor scores of factors of homophobia-obsession, weakness-sensitiveness-indigestion-chillness-skin syndrome, sexual weakness, passive-unsociable personality, introverted personality and rational, personality, were significantly high in So-um (small yin) group of medical students. A factor of warmnes and active-sociable personality were significantly high in Tae-um(big yin)group. Also active-sociable and effective pesonality was partly related with So-yang(small yang)group. Conclusion : These results suggest that those present classification methods inconsistent, that these methods are proving only parts of Sa-sang medical theory, and that objective and scientific studies are needed for reliability and validity of Sa-sang medical theory.

골수이식 후 사이토카인과 골교체 생화학적표지자의 변화 및 상관관계

민우성,강무일,한제호,강성구,오기원,이원영,김혜수,문성대,손현식,신완식,김춘추,윤건호,차봉연,이광우,손호영 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.1

Background : Loss of bone mass is usually detected after BMT. The causes of bone loss are related with gonadal dysfunction and immunosuppressants. Cytokines, especially IL-6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study is to assess the relationship of bone turnover markers and cytokines of peripheral blood and bone marrow before and after allogeneic BMT. Methods : This prospective study included two analyses. The first was a study of 46 BMT recipients, examining the relationship between bone turnover markers and cytokines of serum which were measured before and 1, 2, 3, 4 week and 3 months after BMT. The second was a study of 14 BMT patients, measuring bone marrow plasma cytokines such as IL-6 and TNF-? at post-BMT 3 week and bone turnover marker at the same time to assess the relationship beween two parameters. Results : Serum ICTP, bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. There was positive correlation between serum ICTP and bone marrow IL-6 levels at the post-BMT 3 week with a statistical significance, but the correlation between bone turnover markers and bone marrow TNF-? or peripheral blood cytokines was not found. Conclusion : Our data suggest that the progressive increase of bone resorption after BMT is related with the increase of bone marrow IL-6, which is a potent stimulator of bone resorption in vivo(J Kor Soc Endocrinol 15:85-96, 2000).

LPS로 유도한 RAW 264.7 세포의 염증반응에서 흰민들레의 항염증 효과

김민준 ( Min Jun Kim ),배기상 ( Gi Sang Bae ),최선복 ( Sun Bok Choi ),조일주 ( Il Joo Jo ),김동구 ( Dong Goo Kim ),신준연 ( Joon Yeon Shin ),이성곤 ( Sung Kon Lee ),김명진 ( Myoung Jin Kim ),박성주 ( Sung Joo Park ),송호준 ( Ho Jo 대한본초학회 2014 大韓本草學會誌 Vol.29 No.6

Objectives : Taraxacum coreanum (TC) have been used as a traditional medicine to treat inflammatory diseases and anti-oxidant effect in Korea. However, the anti-inflammatory effect of TC water extract on lipopolysaccharide (LPS)-induced inflammation is not well-known. Therefore, this study was performed to identify the anti-inflammatory effect of TC on LPS induced inflammatory. Methods : RAW 264.7 cells were treated with 500 ng/mL of LPS. Water extracts of TC (0.1, 0.25, 0.5 mg/ml) was treated 1 h prior to LPS. Cell viability was measured by MTT assay. Levels of nitric oxide (NO) were measured with Griess reagent and pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (real-time PCR). We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-κB) activation by western blot. Results : Water Extract from TC itself did not have any cytotoxic effect in RAW 264.7 cells. TC treatment inhibited the production of NO production, and pro-inflamamtory cytokines such as interleukin (IL)-6 and IL-1β on protein and mRNA levels. In addition, TC treatment inhibited the LPS-induced activation of MAPKs such as extracellular signal-regulated kinase1/2 (ERK1/2), p38 kinases (p38), c-Jun NH2-terminal kinase (JNK) and NF-κB. Conclusions : In summary, our result suggest that treatment of TC could reduce the LPS-induced inflammation. Thereby, TC could be used as a protective agent against inflammation. Also, this study could give a clinical basis that TC could be a drug or agent to prevent inflammation.

연구보문 : 자연과학 ; 황산처리에 의한 불투수성 황근 종자의 발아촉진에 관한 연구

서상흠 ( Sang Heum Seo ),박민우 ( Min Woo Park ),장미하 ( Mi Ha Chang ),장일웅 ( Il Ung Jang ),심상인 ( Sang In Shim ),나영왕 ( Young Wang Na ),김수영 ( Soo Young Kim ),김석현 ( Seok Hyeon Kim ) 한국국제농업개발학회 2012 韓國國際農業開發學會誌 Vol.24 No.3

The reason of poor germination rate of hamabo mallow seed was speculated using TZ test to determine the viability of seed. Seeds showed high viability via TZ test were not germinated well. The quiescent seeds did not imbibed properly due to the hard seed coat and did not show further processes required for germination. Several well-known treatments for seed coat loosening and water uptake into seed were applied and compared for their efficiency. Stratification, hot water treatment, seed coat scarification, wet-cold treatment were revealed as less effective for improving germination although those treatments were common method for breaking dormant seed. Chemical scarification with sulfuric acid, however, effectively increased germinability and promptness index of hamabo mallow seeds. Optimal time for sulfuric acid treatment was 20 min. Seeds treated for 20 min showed improved germination percentage, germination speed, and promptness index of 80%, 13, and 1969 at 30 days after imbibition, respectively, in petri dish experiment. The values were greater than control seeds showed low values (12%, 1, and 183, respectively). The similar tendency was observed in the pot experiment that sulfuric acid treated seed were sown in artificially mixed soil (loamy soil:peatmoss:sand:compost = 5:2:2:1) and placed in greenhouse. Ultrastructure analysis of chemically scarified seed with sulfuric acid for 20 min by scanning electron microscopy did not show any noticeable changes in seed coat hardness and water uptake via hilum. But the only change after sulfuric acid treatment was removal of hilum cap that close the hilum and hider imbibition. Therefore, subsequent experiment was conducted to know the relationship between removal of hilum cap and facilitated imbibition by sulfuric acid treatment and whether the hilum cap removal directly influenced to the opening of micropyle. Water uptake velocity of seed treated for 20 min in concentrated sulfuric acid for was greater than control seed. This result implies that the crucial effect of sulfuric acid treatment is the removal of hilum cap that increase water uptake via micropyle in hamabo mallow.