IL-15에 의한 류마티스관절염 환자 활막 섬유모세포에서의 SDF-1 유도

박영은 ( Young Eun Park ),김성일 ( Sung Il Kim ),박성후 ( Seong Hu Park ),백승훈 ( Seung Hoon Baek ),오혜좌 ( Hye Jwa Oh ),허양미 ( Yang Mi Heo ),조미라 ( Mi La Cho ) 대한류마티스학회 2010 대한류마티스학회지 Vol.17 No.3

Objective: Interleukin-15 (IL-15) recruits and activates synovial T cells, and IL-15 plays an important role in amplifying and perpetuating inflammation in the pathogenesis of rheumatoid arthritis (RA). Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for memory T cells in the inflamed RA synovium. This study investigated the effect of IL-15 on SDF-1 production in RA fibroblast-like synoviocytes (FLS). Methods: The expressions of IL-15 and SDF-1 were determined from the synovium of patients with RA and osteoarthritis (OA) by performing immunohistochemistry. The expressions of SDF-1 was measured from the RA FLS that were cultured with IL-15 and IL-17 by real-time RT-PCR and ELISA. The SDF-1 expression was also measured, via ELISA, from the RA FLS stimulated by IL-15 together with the inhibitors of such intracellular signal molecules as phosphatidylinositol 3-kinase (PI 3-kinase, LY294002), STAT3 (AG490), MAP Kinase (PD98059), NF-κB (parthenolide) and activator protein 1 (AP-1, curcumin). Results: IL-15 and SDF-1 were mainly expressed in the RA synovium compared to that of the OA synovium. IL-15 increased the SDF-1 expressions and it, and had an additive effect with IL-17 on the SDF-1 expressions in the cultured RA FLS. The IL-15 induced increase of the SDF-1 expression in the cultured RA FLS was blocked by the inhibitors of PI 3-kinase, NF-κB and AP-1. Conclusion: The SDF-1 expression was increased in the RA synovium and it was up-regulated by IL-15 in the RA FLS through the PI 3-kinase, NF-κB, and AP-1 pathways. These results imply that the IL-15 induced increase of the SDF-1 expressions may be involved in the immunopathogenesis of RA.

위암에서 Helicobacter pylori cagA, vacA, iceA 유전자와 숙주 Interleukin-1β및 Interleukin-1 수용체 길항제 유전자 다형성

이성훈 ( Seong Hun Lee ),김태오 ( Tae Oh Kim ),이동현 ( Dong Hyun Lee ),박원일 ( Won Il Park ),김광하 ( Gwang Ha Kim ),허정 ( Jeong Heo ),강대환 ( Dae Hwan Kang ),송근암 ( Geun Am Song ),조몽 ( Mong Cho ) 대한내과학회 2006 대한내과학회지 Vol.71 No.1

Background: Both Helicobacter pylori (H. pylori) cagA, vacA, iceA genotype and host IL-1B/IL-1RN polymorphisms play a role in determining the clinical consequences of H. pylori infection. This study aimed to investigate whether there might be any combinations of H. pylori cagA, vacA, iceA genotype and host IL-1B/IL-1RN polymorphisms that are particularly associated with the occurrence of gastric carcinoma in Korean patients. Methods: This study population was comprised of 239 patients with H. pylori infection: 122 with gastric carcinoma and 117 with gastritis only. DNA was isolated from gastric biopsy sample and H. pylori cagA, vacA and iceA genotype were determined by PCR. IL-1B-511 polymorphisms were genotyped by PCR-RFLP and IL-1RN polymorphisms were analyzed with variable number of tandom repeat after PCR. Results: H. pylori cagA, vacA, and iceA genotype were not associated with an increased risk for gastric carcinoma. IL-1B-511*T carriers and IL-1RN*2 carriers did not show increased risk for gastric carcinoma. On combination of bacterial/host genotypes, cagA+/IL-1B-511*T carriers and cagA+/IL-1RN*2 carriers, vacA s1/IL-1B-511*T carriers, vacA s1/IL-1RN*2 carriers, vacA m1/IL-1B-511*T carriers, vacA m1/IL-1RN*2 carriers, iceA1/IL-1B-511*T carriers, iceA1/IL-1RN*2 carriers showed no increased risk of gastric carcinoma. Conclusions: Combined H. pylori cagA, vacA, iceA genotype and host IL-1B/IL-1RN polymorphisms shows no increased risk of gastric carcinoma. Therefore, it seems other endogenous or exogenous factors may play more important role in the development of gastric carcinoma in Korean.(Korean J Med 71:24-37, 2006)

Association of DOCK8, IL17RA, and KLK12 Polymorphisms with Atopic Dermatitis in Koreans

( Won Il Heo ),( Kui Young Park ),( Mi-kyung Lee ),( Yu Jeong Bae ),( Nam Ju Moon ),( Seong Jun Seo ) 대한피부과학회 2020 Annals of Dermatology Vol.32 No.3

Background: Early-onset and severe atopic dermatitis (AD) in patients increase the probability of the development of allergic rhinitis or asthma. Treatment and prevention strategies in infants and young children with AD are targeted toward treating the symptoms, restoring skin barrier functions, and reducing the absorption of environmental allergens in an attempt to attenuate or block the onset of asthma and food allergy. Objective: Given that the initiating events in AD remain poorly understood, identifying those at risk and implementing strategies to prevent AD is necessary. Methods: Whole-exome sequencing (WES) was performed in a 43 control group and a disease group with 20 AD patients without atopic march (AM) and 20 with AM. Sanger sequencing was carried out to validate found variants in cohorts. Results: DOCK8, IL17RA, and KLK12 single-nucleotide polymorphisms were identified by WES as missense mutations: c.1289C>A, p.P97T (rs529208); c.1685C>A, p.P562G (rs12484684); and c.457+27>C, rs3745540, respectively. A case-control study show that total immunoglobulin E (IgE) level was significantly increased in the AA genotype of DOCK8 compared to the CA genotype in allergic patients. The rs12484684 of IL17RA increased risk of adult-onset AD (odds ratio: 1.63) compared to the control for (A) allele frequency. AD and AM Patients with the IL17RA CA genotype also had elevated IgE levels. rs3745540 of KLK12 was associated with AD in dominant model (odds ratio: 2.86). Conclusion: DOCK8 (rs529208), IL17RA (rs12484684), and KLK12 (rs3745540), were identified using a new WES filtering method. the result suggests that polymorphism of DOCK8 and IL17RA might be related to increase the total IgE level. (Ann Dermatol 32(3) 197∼205, 2020)

Involvement of IL-10 gene promoter polymorphisms in the susceptibility for childhood asthma.

Kim, Kyung Won,Lee, Kyung Eun,Hong, Jung Yeon,Kim, Mi Na,Heo, Won Il,Sohn, Myung Hyun,Kim, Kyu-Earn Springer International 2011 Lung Vol.189 No.5

<P>Asthma and atopy have a complex background that may result from the interaction of genes and the environment. Interleukin (IL)-10 is known to play various roles in immune-regulating and anti-inflammatory responses. The aim of this study was to evaluate the possible effect of the IL-10 promoter polymorphisms on susceptibility to childhood asthma. We recruited 333 patients with atopic asthma, 55 with nonatopic asthma, and 248 normal controls. We performed a genetic association study of three genetic polymorphisms (IL-10 -1082A>G, IL-10 -819T>C, and IL-10 -592A>C) of the IL-10 promoter. There was no difference between atopic asthma, nonatopic asthma, and normal controls with respect to allele, genotype, or haplotype frequencies of these IL-10 polymorphisms. However, the -1082A>G polymorphism and ATA haplotype in the IL-10 promoter gene were associated with airway hyper responsiveness (AHR) and the -819T>C, -592A>C, and ATA and ACC haplotypes were also shown to be related to serum eosinophil cationic protein (ECP). Our results suggest that the polymorphisms within the IL-10 promoter may have a disease-modifying effect in the asthmatic airway.</P>

Tumor Necrosis Factor-α-Activated Human Adipose Tissue–Derived Mesenchymal Stem Cells Accelerate Cutaneous Wound Healing through Paracrine Mechanisms

Heo, Soon Chul,Jeon, Eun Su,Lee, Il Hwan,Kim, Hoon Soo,Kim, Moon Bum,Kim, Jae Ho The Society for Investigative Dermatology, Inc 2011 The Journal of investigative dermatology Vol.131 No.7

Human adipose tissue–derived mesenchymal stem cells (ASCs) stimulate regeneration of injured tissues by secretion of various cytokines and chemokines. Wound healing is mediated by multiple steps including inflammation, epithelialization, neoangiogenesis, and proliferation. To explore the paracrine functions of ASCs on regeneration of injured tissues, cells were treated with tumor necrosis factor-α (TNF-α), a key inflammatory cytokine, and the effects of TNF-α-conditioned medium (CM) on tissue regeneration were determined using a rat excisional wound model. We demonstrated that TNF-α CM accelerated wound closure, angiogenesis, proliferation, and infiltration of immune cells into the cutaneous wound in vivo. To assess the role of proinflammatory cytokines IL-6 and IL-8, which are included in TNF-α CM, IL-6 and IL-8 were depleted from TNF-α CM using immunoprecipitation. Depletion of IL-6 or IL-8 largely attenuated TNF-α CM-stimulated wound closure, angiogenesis, proliferation, and infiltration of immune cells. These results suggest that TNF-α-activated ASCs accelerate cutaneous wound healing through paracrine mechanisms involving IL-6 and IL-8.

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.

8주간의 유산소성 체조활동을 통한 뇌병변 장애인의 체력 및 염증반응지표 변화

허금 ( Keum Heo ),김광준 ( Kwang Jun KIm ),김권일 ( Kwon Il Kim ),박동호 ( Dong Ho Park ),전태원 ( Tae Won Jun ),송욱 ( Wook Song ) 한국특수체육학회 2009 한국특수체육학회지 Vol.17 No.4

본 연구의 목적은 뇌병변 장애인을 대상으로 8주간의 유산소성 체조활동을 실시하여 신체조성, 체력 및 염증반응지표의 변화에 대하여 알아보는 것이다. 본 연구의 피험자는남·녀 뇌병변장애 중 대표적인 뇌졸중 장애인 17명을 대상으로 시작되었지만 9명이 중도포기하여 최종 8명이 참가하였다. 운동 프로그램 참여 전 사전 검사를 실시하였으며, 기본적 변인으로 신장, 체중, Body Mass Index(BMI), 안정시 심박수, 안정시 혈압을 측정하고, 체력 변인으로는 체간 굴곡과 신전, 견관절 굴곡과 신전의 유연성과 악력을 통한근력, 폐활량을 통한 폐기능을 측정하였다. 또한 혈액성분으로는 혈중지질, 그리고 심혈 관질환 위험인자인 염증반응지표로서 C-reactive protein(CRP), Interleukin-6(IL-6), Tumor Necrosis Factor-α(TNF-α)를 분석하였다. 8주 유산소성 체조활동 프로그램은 매회50분씩 주 2회 실시하였으며, 운동강도는 운동자각도(RPE) 수준 13으로 유지하였다. 뇌병변 장애인의 유산소성 체조활동 프로그램 참여 후 운동의 효과를 검증한 결과 전체 집단에서 안정시 수축기혈압과 이완기혈압이 유의하게 감소하였다(p<.01). 또한 체력 요인에서는 체간 굴곡과 신전(p<.05), 건측의 견관절 굴곡과 신전(p<.01), 환측의 견관절 굴곡(p<.05)이 유의하게 증가하였다. 혈액 성분의 분석 결과 혈중지질에는 유의한 변화가 나타나지 않았으며, 염증반응지표의 경우 IL-6가 유의하게 감소하였고(p<.05), 유의하지는 않으나 CRP도 감소하는 경향을 나타냈다(p<.088). 결론적으로, 지속적이고 규칙적인 유산소성 체조활동은 뇌병변 장애인의 안정시 심박수와 혈압 및 체력을 개선시키는 효과가 있을 뿐만 아니라 심혈관질환의 위험요소로 알려져 있는 염증반응지표를 개선하는 데에도 긍정적인 영향을 주는 것으로 나타났다. The purpose of this study was to analysis the effect of aerobic gymnastic exercise for eight weeks on physical fitness and inflammatory markers which are known as risk factors for cardiovascular diseases in hemiplegic disabled after cerebral stroke. For this purpose, stroke patients(n=8) participated in aerobic exercise training 2 days/week, 50 mins/day, for 8 weeks and maintained at 13 level of RPE. Body composition, resting heart rate and blood pressure were measured before physical fitness test. Trunk flexion/extension, shoulder flexion/extension, grip strength, pulmonary function were measured as physical fitness test. Blood sample of 15ml was drawn from antecubital veins for measuring inflammatory markers(c-reactive protein, interleukin-6, tumor necrosis factor-α). The result of this study is as follows: Resting blood pressure decreased significantly after 8-week aerobic exercise training in total stroke patients (p<.01). After completion of the aerobic exercise program, trunk extension/flexion(p<.05), shoulder extension/fexion(p<.01), were significantly improved in total stroke patients. There was no significant improvement on blood lipid profiles in total stroke patients. However, IL-6 was significantly improved in stroke patients after 8-week aerobic exercise(p<.05). In conclusion, These findings suggests that regular aerobic gymnastic exercise decreases resting heart rate and blood pressure, and improves physical fitness, inflammatory markers which are known as a risk factor of cardiovascular diseases in person with disability occurred due to hemiparetic stroke

Anti-inflammatory effect of polyphenol-rich extract from the red alga Callophyllis japonica in lipopolysaccharide-induced RAW 264.7 macrophages

Ryu, BoMi,Choi, Il-Whan,Qian, Zhong-Ji,Heo, Soo-Jin,Kang, Do-Hyung,Oh, Chulhong,Jeon, You-Jin,Jang, Chul Ho,Park, Won Sun,Kang, Kyong-Hwa,Je, Jae-Young,Kim, Se-Kwon,Kim, Young-Mog,Ko, Seok-Chun,Kim, G The Korean Society of Phycology 2014 ALGAE Vol.29 No.4

Despite the extensive literature on marine algae over the past few decades, a paucity of published research and studies exists on red algae. The purpose of this study was to evaluate the potential therapeutic properties of the ethanol extract of the red alga Callophyllis japonica against lipopolysaccharide (LPS)-stimulated macrophage inflammation. The C. japonica extract (CJE) significantly inhibited the nitric oxide (NO) production and the induced dose-dependent reduction of the protein and mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. Additionally, the CJE reduced the mRNA levels of inflammatory cytokines, including tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6. We investigated the mechanism by which the CJE inhibits NO by examining the level of mitogen-activated protein kinases (MAPKs) activation, which is an inflammation-induced signaling pathway in macrophages. The CJE significantly suppressed the LPS-induced phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38 MAPK. Taken together, the results of this study demonstrate that the CJE inhibits LPS-induced inflammation by blocking the MAPK pathway in macrophages.

The Role of Collagen VI α6 Chain Gene in Atopic Dermatitis

( Hye Jung Jung ),( Won Il Heo ),( Kui Young Park ),( Mi-kyung Lee ),( Ji Young Ahn ),( Mi Youn Park ),( Seong Jun Seo ) 대한피부과학회 2022 Annals of Dermatology Vol.34 No.1

Background: In a previous study, we carried out whole-exome sequencing to identify genetic variants associated with early onset atopic dermatitis (AD) in Koreans and found that collagen VI α6 chain (COL6A6) gene polymorphisms are associated. COL6A6 is one of the chains that makes up the triple helix of collagen VI, and little is known about its role in AD. Objective: To identify how COL6A6 changes in AD and clarify its role. Methods: Immunohistochemical staining for COL6A6 was performed on tissues of AD, other skin diseases, and healthy controls. Human keratinocytes and fibroblasts were exposed to inflammatory cytokines and cultured to evaluate changes in COL6A6 expression. COL6A6 small interfering RNA (siRNA) was transfected into cells to identify the role of COL6A6. Results: Total COL6A6 mRNA was higher in AD than in controls. In AD tissues, COL6A6 mRNA decreased significantly in the epidermis compared to controls, whereas COL6A6 protein was increased in the dermis. In the cultured cells, COL6A6 mRNA was suppressed in the epidermis by interleukin (IL)-4 and IL-13, whereas COL6A6 protein was induced in the dermis. In the COL6A6 siRNA-transfected keratinocyte, mRNA of FLG, LOR, and CASP14 decreased compared to controls; in contrast, mRNA of MMP1 increased. Conclusion: The reduction of epidermal COL6A6 due to the genetic mutation can cause skin barrier damage and it can contributes to the early onset of AD. COL6A6 is induced by IL-4 and IL-13, and it may play a role in fibrotic remodeling and inflammatory processes, which are major features of AD.

Adenine attenuates lipopolysaccharide-induced inflammatory reactions

Silwal, Prashanta,Lim, Kyu,Heo, Jun-Young,Park, Jong IL,Namgung, Uk,Park, Seung-Kiel The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.4

A nucleobase adenine is a fundamental component of nucleic acids and adenine nucleotides. Various biological roles of adenine have been discovered. It is not produced from degradation of adenine nucleotides in mammals but produced mainly during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine have been supported in IgE-mediated allergic reactions, immunological functions of lymphocytes and dextran sodium sulfate-induced colitis. However adenine effects on Toll-like receptor 4 (TLR4)-mediated inflammation by lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not examined. Here we investigated anti-inflammatory roles of adenine in LPS-stimulated immune cells, including a macrophage cell line RAW264.7 and bone marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines $TNF-{\alpha}$ and IL-6 and inflammatory lipid mediators, prostaglandin $E_2$ and leukotriene $B_4$. Adenine impeded signaling pathways eliciting production of these inflammatory mediators. It suppressed $I{\kappa}B$ phosphorylation, nuclear translocation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$), phosphorylation of Akt and mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production of $TNF-{\alpha}$, IL-6 and IL-13 and also hindered phosphorylation of $NF-{\kappa}B$ and Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of $TNF-{\alpha}$ and IL-6 by peritoneal cells in mice. These results show that adenine attenuates the LPS-induced inflammatory reactions.