호산구의 활성 억제 사이토카인과 억제 기작의 규명

박춘식 ( Park Chun Sig ),최은남 ( Choe Eun Nam ),이영목 ( Lee Yeong Mog ),박성우 ( Park Seong U ),장안수 ( Jang An Su ),이준혁 ( Lee Jun Hyeog ),최윤성 ( Choe Yun Seong ),정일엽 ( Jeong Il Yeob ) 대한천식알레르기학회 2003 천식 및 알레르기 Vol.23 No.4

Interleukin-1B(1L-1B) polymorphisms and gastric mucosal levels of IL-Iβ cytokine in Korean patients with gastric cancer

Chang, Young-Woon,Jang, Jae-Young,Kim, Nam-Hoon,Lee, Jae Won,Lee, Hyo Jung,Jung, Woon Won,Dong, Seok-Ho,Kim, Hyo-Jong,Kim, Byung-Ho,Lee, Joung-Il,Rin Chang KYUNG HEE UNIVERSITY MEDICAL CENTER 2006 고황의학상 수상논문집 Vol.21-22 No.-

Interleukin-1B and IL-1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL-1B-511T polymorphism and the risk of GC in Asians. We tested for an association between IL-1 loci polymorphisms with increased gastric mucosal levels of IL-1β and an increased risk of developing GC in a Korean population. Polymorphisms of IL-1A-889, IL-1B-31, IL-1B-511 and IL-1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL-1β cytokine was measured using an ELISA. The frequencies of IL-1A, IL-1B-511, IL-1B-31 and IL-1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal-type GC showed a higher frequency of IL-1B-31T homozygotes (OR = 2.2; 95% CI = 1.1-4.3) compared with controls. Risk was also significantly increased in these patients for IL-1B-31T homozygotes compared with patients with diffuse-type GC (OR = 3.4; 95% CI = 1.5-7.7). As in Caucasian populations, linkage disequilibrium between IL-1B-31 and IL-1B-511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL-1B-31T/IL-1B-511C) was opposite (IL-1B-511T/IL-1B-31C). Mucosal IL-1β levels in H. pylori-infected GC patients were higher in patients homozygous for IL-1B-31T compared with IL-1B-31C/T and IL-1B-31C/C. Thus, the combined effects of H. pylori infection and IL-1B-31T/IL-1B-511C polymorphisms with enhanced mucosal IL-1β production contributed to the development of intestinal-type GC in this Korean population.

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.

폐포 대식세포 및 단핵구가 Interleukin-2 Enhanced Natural Killer 및 LAK Activity에 미치는 영향

조철호 ( Jo Cheol Ho ),김병일 ( Kim Byeong Il ),김세규 ( Kim Se Gyu ),천선희 ( Cheon Seon Hui ),김형중 ( Kim Hyeong Jung ),장준 ( Jang Jun ),안철민 ( An Cheol Min ),김성규 ( Kim Seong Gyu ),이원영 ( Lee Won Yeong ),윤정구 ( Yun J 대한내과학회 1992 대한내과학회지 Vol.42 No.5

저자들은 폐포 대식세포 및 말초혈액내의 단핵구가 NK 활성도 및 LAK 활성도에 미치는 영향을 보기위하여, 임파구에 여러 가지 농도(0, 100 : 1, 10 : 1, 1 : 1)의 폐포 대식세포와 단핵구를 넣어 IL-2 enhanced NK 활성도 및 LAK 활성도를 비교하여 다음과 같은 결과를 얻었다. 1) 여러 가지 농도의 단해구는 IL-2 enchanced NK 활성도 및 LAK 활성도에 영향을 미치지 않았다. 2) 동량의 페포대식세포(임파구 : 폐포 대식세포= 1 : 1)는 IL-2 enhanced NK 활성도를 의의있게 억제하였으나(p<0.05), 소량의 폐포대식세포(임파구 : 폐포 대식세포-10 : 1과 100 : 1)는 IL-2 enhanced NK 활성도를 억제하지 못하였다. 3) 임팍와 폐포 대식세포의 비율이 1 : 1과 10 : 1에서는 LAK 활성도를 의의있게 억제하였으나, 소량의 폐포대식세포(임파구 : 폐포 대식세포=100 : 1)는 LAK 활성도를 억제하지 못하였다(p<0.05). 이상의 결과로 IL-2 enhanced NK 활성도 및 LAK 활성도는 폐포 대식세포의 양에 비례하여 억제되었으나, 말초혈액내의 단핵구에 의해서는 영향받지 않는 것을 알 수 있었다. Alveolar macrophages (AM) are thought to function as primary effector cells against tumors growing in the lung. Systemic administration of lymphokine activated killer (LAK) cells and IL-2 resulted in partial antitumor response in patients with advanced cancer. LAK activity is influenced by various factors. We studied the effects of AM and blood monocytes from healthy donors on IL-2 enhanced NK activity against K-562 cells and LAK activity against Raji cells utilizing a 4h ^(51)Cr release assay. The following results were obtained: 1) The addition of different doses of human blood monocytes showed no suppression or enhancement of IL-2 enhanced NK and LAK activity. 2) The addition of high dose of AM (Lymphocyte: AM=1:1) significantly suppressed IL-2 enhanced NK activity. Smaller doses of AM (Lymphocyte: AM= 10:1and 100:1) did not suppress IL-2 enhanced NK activity. 3) The addition of high dose of AM (Lymphocyte: AM = 1:1 and 10:1) significantly suppressed LAK activity. The smallest dose of AM (Lymphocyte: AM= 100:1) did not suppress LAK activity. In conclusion, IL-2 enhanced NK and LAK activity were dose-dependently suppressed by human alveolar macrophages. However IL-2 enhanced NK and LAK activity were not suppressed by blood monocytes.

Activation of Transient Receptor Potential Melastatin Family Member 8 (TRPM8) Receptors Induces Proinflammatory Cytokine Expressions in Bronchial Epithelial Cells

김주희,Young Sook Jang,Hwan Il Kim,박지영,박성훈,Yong Il Hwang,Seung Hun Jang,Ki-Suck Jung,Hae Sim Park,Choon-Sik Park 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.4

Purpose: Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. Methods: The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. Results: Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. Conclusions: TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.

Regulation of interleukin-11 expression in ovulatory follicles of the rat ovary

Jang, You-Jee,Park, Jae-Il,Jeong, Seong-Eun,Seo, You-Mi,Dam, Phuong T. M.,Seo, Young-Woo,Choi, Bum-Chae,Song, Sang-Jin,Chun, Sang-Young,Cho, Moon-Kyoung Commonwealth Scientific and Industrial Research Or 2017 Reproduction, fertility, and development Vol. No.

<P> The aim of the present study was to examine the regulation of interleukin (IL)-11 expression, as well as the role of IL-11, during ovulation in gonadotropin-primed immature rats. Injection of equine chorionic gonadotropin (eCG), followed by human CG (hCG) to induce superovulation stimulated expression of the Il11 gene in theca cells within 6 h, as revealed by northern blot and in situ hybridisation analyses. Real-time reverse transcription-polymerase chain reaction analysis showed that the IL-11 receptor, α subunit gene was expressed in granulosa and theca cells and that injection of hCG had no effect on its expression. IL-11 protein expression was stimulated in theca cells by hCG. LH-stimulated increases in Il11 mRNA levels in cultured preovulatory follicles were inhibited by protein kinase A and mitogen-activated protein kinase kinase inhibitors. Toll-like receptor (TLR) 2 and TLR4 were detected in preovulatory follicles, and the TLR4 ligand lipopolysaccharide, but not the TLR2 ligand Pam3Cys, increased Il11 mRNA levels in theca cells, but not in granulosa cells. Treatment of preovulatory follicles with IL-11 stimulated progesterone production and steroidogenic acute regulatory protein (Star) gene expression. Together, these results indicate that IL-11 in theca cells is stimulated by mitogen-activated protein kinase signalling and TLR4 activation, and increases progesterone production during ovulation. </P>

Acetyl salicylic acid inhibits Th17 airway inflammation via blockade of IL-6 and IL-17 positive feedback

문형근,Chil Sung Kang,최준표,최동식,Hyun Il Choi,최용욱,전성규,유주연,Myoung Ho Jang,고용송,김윤근 생화학분자생물학회 2013 Experimental and molecular medicine Vol.45 No.1

T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation,which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17positive feedback.

Triptolide suppresses interleukin-1beta-induced human beta-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-kappaB in A549 cells.

Jang, Byeong-Churl,Lim, Ki-Jo,Choi, In-Hak,Suh, Min-Ho,Park, Jong-Gu,Mun, Kyo-Chul,Bae, Jae-Hoon,Shin, Dong-Hoon,Suh, Seong-Il D.A. Spandidos 2007 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.19 No.5

<P>The immunosuppressive effect of triptolide has been associated with suppression of T-cell activation. However, the immunosuppressive effects of triptolide on innate immunity in the epithelial barrier remain to be elucidated. Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide and plays an important role in the innate immunity. We have previously demonstrated that IL-1beta induced HBD-2 mRNA expression in A549 cells through activation of nuclear factor-kappaB (NF-kappaB) transcriptional factor as well as p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), or phosphatidylinositol-3-kinase (PI3K). In this study, we investigated effects of triptolide on IL-1beta-induced HBD-2 mRNA expression in A549 cells. Triptolide inhibited IL-1beta-induced HBD-2 mRNA expression in a dose-dependent manner. Addition of triptolide did not suppress activation of p38 MAPK, JNK, or PI3K in response to IL-1beta. Triptolide inhibited IL-1beta-induced MAPK phosphatase-1 expression at the transcriptional level and resulted in sustained phosphorylation of JNK or p38 MAPK, explaining the little effect of triptolide on IL-1beta-induced phosphorylation of these kinases. Although triptolide partially suppressed IL-1beta-mediated degradation of IkappaB-alpha and nuclear translocation of p65 NF-kappaB, triptolide potently inhibited NF-kappaB promoter-driven luciferase activity in A549 cells. These results collectively suggest that the inhibitory effect of triptolide on IL-1beta-induced HBD-2 mRNA expression in A549 cells seems to be at least in part mediated through nuclear inhibition of NF-kappaB transcriptional activity, but not inhibition of p38 MAPK, JNK, or PI3K. This inhibition may explain the ability of triptolide to diminish innate immune response.</P>

DBA1J 마우스에서 가감보중익기탕이 콜라젠 유도 관절염 억제에 미치는 효과

장선일 ( Jang Seon Il ),윤용갑 ( Yun Yong Gab ) 대한본초학회 2003 大韓本草學會誌 Vol.18 No.3

N/A Objectives : The present study has been undertaken to investigate the effect of Kagam-Bojungikgitang (KBT) decoction on development of collagen-induced arthrtis (CIA) in DBAl J mice. Methods : CIA was induced in UBAJ1 mice by immunization with bovine type II collagen (CIU and treatment with lipopolysacchride (LPS). KBT is the water extracts prepared from Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Astractylodis Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Artemisiae iwayomogii Herba, Scutellariae Radx. This is a modifitd prescription of Bojungikgitang, which has been used for the treatment of indigestion, and immunological disease in oriental countries. KBT was orally administered at difference doses. The incidence of arthritis, arthritis index, levels of tumor necrosis factor -alpha (TNF-a). interferon-gama (IFN-V), interleukin lbeta (IL-lP), IL - 3 . IL--10, II- 13. and prostaglandin E? (PGE.1 and cyclooxygenase~-2 (COX21 activity were investigated. Results : KBT dose- dependently suppressed the release of T h l cytokines (TNF-a, IFN-.v, and IL-1 8 ) and inflammatory mediators (PGE? and COX--2 caused by immunization of CII and stimulation of 1,PS. KUT without cytotoxic effext. Kagam-bojunyikgitang`s Inhibitory effects were better than Ehjungikgitang in PGEz production and COX-2 expression. However, KBT increased markedly the production of Th:! cytokines (IL-4, IL 10, and IL -13). Therefor , KBT suppressed markedly the incidence of arthritis and arthritis index caused by immunization of CII and stimulation of LPS. Conclusion : These results suggest that KBT suppress inflammatory mediators and regulates Th l and Th2 cytokmes. And these properties may contribute to the strong anti-arthritis of KBT.

2,3-Dehydrosilybin Suppresses IL-31-Associated Pruritus Factors in Astrocytes and Microglia

Ji Hyeon Park,Jae Young Shin,Feng Wang,Suping Hao,Da Jeong Shin,Seon Il Jang,Byoung Ok Cho 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Chronic pruritus is the main symptom that increases the suffering of patients in hypersensitivity disorder disease. IL-31 is a pruritic cytokine with a primary objective to control itch. A 2,3-dehydrosilybin (DHS) is a type of flavonoid extracted from the seeds of milk thistle. DHS has been reported to have hepatoprotective, angiogenic, and antioxidant effects. This study investigated the effect of DHS pretreatment on IL-31-associated pruritus in astrocytes and microglia. Pretreatment with DHS inhibited the production of IL-31 by lipopolysaccharide (LPS) and interferon gamma (IFN-γ) stimulation in microglia. Pretreatment with DHS inhibited the phosphorylation of MAPK, STAT1 and NF-κB by LPS plus IFN-γ stimulation in microglia. In addition, DHS suppressed the expression of IL-31 receptor A in IL-31-treated astrocytes. DHS also inhibited lipocalin2 production in IL-31 stimulated astrocytes. Taken together, DHS has potential as a therapeutic agent for symptom relief by down-regulating the IL-31-mediated pruritus mechanism in microglia and astrocytes.