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.

The enhanced IL-l8 production by UVB irradiation requires ROI and AP-1 signaling in human keratinocyte cell line (HaCaT)

Cho, Daeho,Kang, Jae Seung,Park, Jong Hoon,Kim, Young-In,Hahm, Eunsil,Lee, Junechul,Yang, Yoolhee,Jeon, Junho,Song, HyunKeun,Park, Hyunjeong,Kim, Taesung,Pang, Saic,Kim, Chul-Woo,Hwang, Young Il,Lee, 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-

Based on our recent observation that enhanced IL-18 expression positively correlates with malignant skin tumors, such as SCC and melanoma, we examined the possible role of UVB, known to be associated with skin cancer development, in the enhancement of IL-18 production using primary human epidermal keratinocytes and human cell line HaCaT. After cells were exposed to UVB irradiation in vitro, IL-18 production was examined by Northern blot analysis and ELISA, and it was found that IL-18 production is enhanced by UVB irradiation in a dose- and time-dependent manner. In addition, we confirmed that it is functionally active form of IL-18 using the inhibitor of caspase-1. The effect of UVB irradiation was blocked by antioxidant, N-acetyl-ι-cysteine (NAC), which suggested the involvement of reactive oxygen intermediates (ROI) in the signal transduction of UVB irradiation-enhanced IL-18 synthesis. We also found that UVB irradiation increased AP-1 binding activity by using EMSA with AP-1-specific oligonucleotide. Furthermore, inhibitors of UVB-induced AP-1 activity, such as PD98059, blocked enhanced IL-18 production, indicating that AP-1 activation is required for UVB-induced IL-18 production. Taken together, our results suggest that UVB irradiation-enhanced IL-18 production is selectively mediated through the generation of ROI and the activation of AP-1.

Evaluation of ‘TNF-α, IL-6, and MMP-9’ Test Kit for Screening of Meibomian Dysfunction in Patients with Inflammatory Dry Eye Syndrome

Min-Hye Park,Jung-Eun Park,Jang-Won Byun,Min-Ji Choi,Il-Hoon Cho,Myeong-Jin Jeong,Yoon-Jung Choy,Koon-Ja Lee 대한시과학회 2020 대한시과학회지 Vol.22 No.1

목적 : 마이봄샘기능저하증(meibomian gland dysfunction, MGD)을 수반하는 염증성 건성안의 감별진단에 대한 ‘TNF-α, IL-6, MMP-9’ 검사키트의 유용성을 평가하였다. 방법 : 건성안 이외의 안질환이 없는 20~30대 중 OSDI 설문 검사에 따른 건성안 총 118안을 대상하였고, 결막낭 메니스커스로부터 소량의 눈물을 채취하여 TNF-α, IL-6 및 MMP-9 검사를 하였다. 각막염색과 결막충혈 이 모두 Grade 1 이상인 경우는 염증성 건성안으로, 마이봄샘폐쇄와 마이봄샘구멍막힘이 모두 grade 1 이상인 경우는 MGD 관련 건성안으로 평가하였다. 염증성 건성안 및 MGD와 TNF-α, IL-6, MMP-9과의 상관성은 카 이제곱검정(Chi-square test)으로 분석하였고, ‘TNF-α, IL-6, MMP-9’ 검사키트의 염증성 건성안과 MGD를 수반하는 염증성 건성안 감별능력은 ROC 커브를 이용하여 민감도, 특이도 및 AUC(Area under the curve)를 구하고 정확도를 평가하였다. 결과 : 염증성 건성안은 TNF-α와 IL-6와 유의한 상관성을 보였고(p<.050), ‘TNF-α, IL-6, MMP-9’ 검사 키트는 MMP-9 검사키트와 80.20%의 높은 일치도를 나타냈으나(p<.050), 염증성 건성안 감별에 대한 민감도, 특이도, 정확도는 MMP-9 검사키트보다 낮았다. MGD는 MMP-9 검사와 상관성을 보이지 않았고, TNF-α와 IL-6 검사와는 유의한 상관성을 보였으며, MGD 감별에 대한 민감도, 특이도, 정확도는 각각 85.50%, 34.70%, 0.601, 85.50%, 32.70%, 0.591로 나타났다. MGD 수반한 염증성 건성안 감별에 대한 ‘TNF-α, IL-6, MMP-9’ 검사키트의 민감도, 특이도 및 정확도는 100.00%, 34.10%, 0.670로 MMP-9 검사키트보다 더 높았다. 결론 : MGD 진단에는 TNF-α, IL-6 검사가 유용하며, ‘TNF-α, IL-6, MMP-9’ 검사키트는 MGD를 수반한 염증성 건성안 평가에 유용할 것으로 사료된다. Purpose : To evaluated the ‘TNF-α, IL-6, MMP-9’ test kit for screening of inflammatory dry eye and IDE (inflammatory dry eye) with MGD (meibomian gland dysfunction). Methods : A total of 118 dry eyes were selected using OSDI (ocular surface disease index) questionnaire among participated 20~30s without ophthalmologic diseases except for dry eye. Small amount of tear obtained from meniscus of the conjunctiva were tested with TNF-α, IL-6, and MMP-9 kit. IDE refers to the criteria which specifies the corneal staining and conjunctival hyperemia more than grade 1 and MGD refers to the criteria which specifies meibomian gland blockage and meibomian orifice obstruction with more than grade 1. Chi-square test was performed to analyze the correlation between the IDE, MGD and the results of ‘TNF-α, IL-6, MMP-9’ tests. and ROC (receiver operate characteristics) curve was used for the sensitivity, specificity and AUC (area under the curve) for the accuracy of ‘TNF-α, IL-6, MMP-9’ tests. Results : TNF-α and IL-6 were significantly correlated with IDE (p<.050) and ‘TNF-α, IL-6, MMP-9’ test kit showed a high agreement of 80.20% with MMP-9 test kit(p<.050) although the accuracy was lower than MMP-9 test kit. The MMP-9 showed no correlation with MGD, however TNF-α, IL-6 were significantly correlated with MGD (p<.050). sensitivity, specificity, and AUC of TNF-α, IL-6 tests for MGD were 85.50%, 34.70%, 0.601, 85.50%, 32.70%, and 0.591. The sensitivity, specificity, and AUC of ‘TNF-α, IL-6, MMP-9’ test kit for IDE with MGD were 100.00%, 34.10%, and 0.670, respectively, which shows higher accuracy than MMP-9. Conclusion : TNF-α and IL-6 tests are useful for the diagnosis of MGD, and ‘TNF-α, IL-6, MMP-9’ test kit is useful for screening IDE with MGD.

Interleukin 17 (IL-17) Increases the Expression of Toll-like Receptor-2, 4, and 9 by Increasing IL-1β and IL-6 Production in Autoimmune Arthritis

LEE, JUN-HEE,CHO, MI-LA,KIM, JU-IN,MOON, YOUNG-MEE,OH, HYE-JWA,KIM, GEUN-TAE,RYU, SUN,BAEK, SEUNG-HOON,LEE, SUN-HEE,KIM, HO-YOUN,KIM, SUNG-IL The Journal of Rheumatology 2009 The Journal of rheumatology Vol.36 No.4

<B>Objective.</B><P>To examine the effect of interleukin 17 (IL-17) on the expression of Toll-like receptor (TLR)-2, 4, and 9 in collagen-induced arthritis (CIA) in mice.</P><B>Methods.</B><P>On Days 28 and 32 after induction of CIA in mice, phosphate-buffered saline (PBS group) or IL-17 (IL-17 group) was injected into both knee joints. On Day 35, mice were sacrificed. The severity of knee joint arthritis, synovial inflammation, and bone destruction was measured by a scoring system using macrography and histological analysis. Synovial expression of TLR-2, 4, 9, IL-17, IL-1ß, tumor necrosis factor-α (TNF-α), and IL-6 was determined by real-time PCR and immunohistochemistry. Synoviocytes of CIA mice were cultured with IL-17 and with neutralizing antibodies to cytokine, and the expression of TLR-2, 4, 9, IL-1ß, TNF-α, and IL-6 was determined by real-time RT-PCR.</P><B>Results.</B><P>In CIA mice, knee arthritis scores, synovial inflammation, bone destruction scores, and expression of synovial TLR-2, 4, and 9, IL-17, IL-1ß, TNF-α and IL-6 were higher in the IL-17 and PBS groups than in normal DBA1 mice. These variables were also significantly higher in the IL-17 group than in the PBS group. In CIA synoviocytes, IL-17 increased the expression of TLR-2, 4, and 9, and this effect was significantly alleviated by neutralizing antibodies to IL-17, IL-1ß, and IL-6.</P><B>Conclusion.</B><P>IL-17 aggravates joint inflammation and destruction, and increases the synovial expression of TLR-2, 4, and 9 by increasing IL-1ß and IL-6. These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1ß and IL-6 production are involved in the IL-17-induced aggravation of arthritis.</P>

특발성 염증성 근육병증 환자에서 IL-17 발현의 증가

백승훈 ( Seung Hoon Baek ),이준희 ( Jun Hee Lee ),김근태 ( Geun Tae Kim ),이정욱 ( Joung Wook Lee ),조미라 ( Mi Ra Cho ),김주인 ( Ju In Kim ),이선희 ( Sun Hee Lee ),김대성 ( Dae Seong Kim ),김성일 ( Sung Il Kim ) 대한류마티스학회 2008 대한류마티스학회지 Vol.15 No.2

Objective: Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases characterized by infiltration of T lymphocytes, monocytes, and macrophages in muscle tissues. Interleukin-17 (IL-17), a Th17 cytokine, has potent pro-inflammatory actions and plays a role in autoimmune diseases. We investigated the expression of IL-17 in muscle tissues of patients with IIMs. Methods: We measured the IL-17 mRNA level of muscle tissues from 14 patients with IIMs (9 patients with dermatomyositis and 5 patients with polymyositis) by real-time RT-PCR and compared with controls. We also performed an immunohistochemical stain to detect IL-17 expression. Results: The expressions of IL-17 were significantly enhanced in IIMs than controls. In immunohistochemistry, IL-17 was expressed in perimysial, endomysial and perivascular infiltrating inflammatory cells. Conclusion: These results suggest that IL-17 plays a role in the immunopathogenesis of IIMs.

Two-Track Medical Treatment Strategy According to the Clinical Scoring System for Chronic Rhinosinusitis

Kim, Dong-Kyu,Kang, Seong Il,Kong, Il Gyu,Cho, Young Hoon,Song, Seul Ki,Hyun, Se Jin,Cho, Sung Dong,Han, Sang-Yoon,Cho, Seong-Ho,Kim, Dae Woo The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.5

<P><B>Purpose</B></P><P>The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application.</P><P><B>Methods</B></P><P>A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators.</P><P><B>Results</B></P><P>The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses.</P><P><B>Conclusions</B></P><P>The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.</P>

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.

고교 축구선수의 경기 후 회복방법의 차이가 혈중 염증, 근 손상 및 피로 지표에 미치는 영향

백승훈(Seung Hoon Paik),백일영(Il Young Paik),서상훈(Sang Hoon Suh),조수연(Su Youn Cho),노희태(Hee Tae Roh) 한국사회체육학회 2014 한국사회체육학회지 Vol.0 No.56

The purpose of the current study was to investigate the effects of different recovery treatments on serum inflammation, muscle damage and fatigue variables after a game of soccer players in high school. The subjects of current study were 10 soccer players in high school without any medical complications. All subjects received both recovery treatments (contrast bath and massage) for once and a control application; therefore, all underwent 3 experimental conditions. Blood sampling taken at rest, at immediately after the match, and at 60 minutes recovery. From the three blood samples, the parameters of inflammation and fatigue were analyzed. Additional blood sampling was taken at 24 hours recovery for the analysis of the long term effect of the applications on the parameters of muscle damage. The concentration of interleukin-6(IL-6), creatine kinase(CK), lactate dehydrogenase (LDH), and lactate were shown to significantly increase at immediately after the match in all experimental conditions(p<.05). For inflammation responses the concentration of IL-6 60min recovery appeared to be significantly lower in contrast bath and massage treatments compared to control treatment(p<.05). Also, for muscle damages the concentration of CK 24h recovery appeared to be significantly lower in massage treatment compared to contrast bath and control treatments(p<.05). On the base of the results of the current study, it is suggested that soccer match can induce increased concentrations of IL-6, CK, LDH and lactate which may influence on inflammation, muscle damage and fatigue. However, contrast bath and massage were beneficial for recovery from muscle damage.

Regulation of UVB-Induced IL-8 and MCP-1 Production in Skin Keratinocytes by Increasing Vitamin C Uptake via the Redistribution of SVCT-1 from the Cytosol to the Membrane

Kang, Jae Seung,Kim, Ha Na,Jung, Da Jung,Kim, Jee Eun,Mun, Ga Hee,Kim, Yeong Seok,Cho, Daeho,Shin, Dong Hoon,Hwang, Young-Il,Lee, Wang Jae Williams & Wilkins 2007 The Journal of investigative dermatology Vol.127 No.3

It is well known that UVB (290–320 nm) induces inflammation in skin by the transcription and release of cytokines and chemokines from skin keratinocytes. In addition, it is considered that intracellular reactive oxygen species (ROS) plays an important role in UVB-induced inflammatory response in the skin. Therefore, we investigated the effect of vitamin C, a potent antioxidant, on the regulation of UVB-induced skin inflammation via the modulation of chemokines production. Vitamin C uptake into keratinocytes is increased by UVB irradiation in a time- and dose-dependent manner through the translocation of sodium-dependent vitamin C transporter-1 (SVCT-1), a vitamin C-specific transporter, from the cytosol to the membrane. To evaluate the effect of vitamin C on the chemokine mRNA expression, we performed RNase protection assay. As a result, there was a remarkable change in chemokine mRNA expression, especially IL-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, increased IL-8 and MCP-1 mRNA expressions were suppressed by vitamin C treatment. We also confirmed the results of protein levels measured by ELISA. Taken together, vitamin C uptake is increased in UVB-irradiated keratinocytes through the translocation of SVCT-1 and regulates inflammatory response in the skin via the downregulation of IL-8 and MCP-1 production.Journal of Investigative Dermatology (2007) 127, 698–706. doi:10.1038/sj.jid.5700572; published online 28 September 2006

Expression of TLR2, TLR4, and TLR9 in dermatomyositis and polymyositis

Kim, Geun-Tae,Cho, Mi-La,Park, Young-Eun,Yoo, Wan Hee,Kim, Jung-Hee,Oh, Hye-Jwa,Kim, Dae-Sung,Baek, Seung-Hoon,Lee, Sun-Hee,Lee, Jun-Hee,Kim, Ho-Youn,Kim, Sung-Il Springer-Verlag 2010 CLINICAL RHEUMATOLOGY Vol.29 No.3

<P>The aim of this study was to investigate the expressions of Toll-like receptor (TLR) 2, TLR4, TLR9, and their correlations with the expression of cytokines that are associated with activation of CD4<SUP>+</SUP> T cells and inflammation including interferon γ (IFNγ), interleukin 4 (IL4), interleukin 17 (IL17), and tumor necrosis factor α (TNFα) in muscle tissues of patients with dermatomyositis (DM) and polymyositis (PM). The expressions of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were measured by real-time reverse transcription–polymerase chain reaction in muscle tissues from 14 patients with DM and PM (nine patients with DM, five patients with PM) and three controls. The expressions of TLR2, TLR4, and TLR9 were also localized with immunohistochemistry. The expression levels of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were significantly high in patients with DM and PM compared with those in the controls, and the expression levels of TLR4 and TLR9 had significant positive correlations with the expressions of IFNγ, IL4, IL17, and TNFα. Immunohistochemistry showed that TLR2, TLR4, and TLR9 were expressed by infiltrating cells of perimysium in DM, whereas they were expressed by infiltrating cells of endomysium in PM. These results suggest that the involvement of TLR4 and TLR9 in immunopathogenesis of DM and PM might be connected with activation of CD4<SUP>+</SUP> T cells.</P>