카드뮴과 아연이 사람 단핵구성 세포주(THP-1)에서 IL-6의 분비에 미치는 영향

신동훈,서성일,서석권 大韓産業醫學會 1999 대한직업환경의학회지 Vol.11 No.3

Objectives : This study was performed to investigate effects of cadmium and zinc on IL-6 secretion using human monocyte in a culture system. Methods : We have used trypan blue dye exclusion methods to examine the effect of cytotoxicity of CdCl₂, ZnCl₂in THP-1 cells. IL-6 was measured by the ELISA method in the cell culture supernatants and the expression of IL-6 mRNA was examined by reverse transcription-polymerase chain reaction. Results : IL-6 production by THP-1 cells were decreased at 0.1 mM cadmium concentration (p<0.05) and increased as zinc concentration increased. Zinc prevented cadmium-induced suppression of IL-6, and the addition of a chelating agent, EDTA, restores IL-6 secretion. The expression of IL-6 mRNA decreased at 0.08 mM and 0.1 mM cadmium concentrations. Conclusion : This results suggest that cadmium depressed production and gene expression of IL-6 in stimulated human monocytes, and zinc prevented cadmium-induced suppression of IL-6.

Interleukin-17이 배양된 류마티스관절염 활막세포에서 vascular endothelial growth factor 생성에 미치는 영향

곽임수 ( Ihm Soo Kwak ),남태수 ( Tae Soo Nam ),나하연 ( Ha Yeon Rha ),서정탁 ( Jeung Tak Suh ),김유선 ( Yoo Sun Kim ),김성일 ( Sung Il Kim ) 대한류마티스학회 2001 대한류마티스학회지 Vol.8 No.3

Objective: To investigate the the effects of interleukin-17 (IL-17) on the production of vascular endothelial growth factor (VEGF) from cultured rheumatoid arthritis synoviocytes. Methods: Fibroblast-like synovial cells(FLS) were prepared from the synovial tissues of rheumatoid arthritis patients and cultured in the presence of IL-17, IL-17 with or without transforming growth factor-β(TGF-β), tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β). VEGF levels were determined in the culture supernatants by sandwitch ELISA. Results: Stimulation of FLS by serial concentration of IL-17, TGF-β, TNF-α, IL-1β increased the production of VEGF by 2.1-2.7, 2.2-3.0, 2.0-2.9, 2.3-3.1 fold over the constitutive levels of unstimulated FLS. Stimulation of FLS by IL-17 with TGF-β or TNF-α or IL-1β also increased the production of VEGF according to culture periods by 1.6-1.8, 1.1-1.9, 1.5-1.7 fold over the levels stimulated with TGF-β or TNF-α or IL-1β, respectively. This results indicated that IL-17 increased the effect of TGF-β, TNF-α, IL-1β on FLS, leading synergistic enhancement of VEGF production. Conclusion: IL-17 may be involved in the neovascularization in rheumatoid synovitis by enhancing the production of VEGF.

정신분열병과 22번 염색체 인터루킨-2 수용체 β-chain 유전자의 연관성

김용구,이민수,김 인,곽동일,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.3

연구배경 : 정신분열병이 유전적이라고 제시하는 많은 역학 연구와 유전자 연구에도 불구하고, 이 질환의 유전방식과 질병유전자는 밝혀져 있지 않다. 본 연구에서는 정신분열병과 22번 염색체 장완의 11.2-12부위에 위치한 Interleukin-2수용체 β chain 유전자간에 유전적 연합을 조사하고자 정신분열병 환자 93명과 정상대조군 97명 대상으로 중합효소연쇄반응을 이용하여 Interleukin-2 수용체 β chain (IL-2Rβ) 유전자의 다형성 분포를 조사하였다. 연구방법 : 환자군은 DSM-Ⅲ-R 진단기준에 따라 임상아형(망상형, 붕괴형, 미붕괴형, 잔류형)으로 분류하였다. 음성 및 양성 정신분열병으로 분류하기위해 Positive and Negative Syndrome Scale(PANSS)을 사용하였다. Genomic DNA를 전혈 임파구에서 추출한 후, IL-2Rβ 유전자좌를 분석하기 위해 dinucleotide(GT)n 염기배열순서를 중합효소연쇄반응을 이용하여 증폭시켰다. 연구결과 : IL-1Rβ의 대립유전자는 모두 8가지 종류이고, guanine-thymine의 반복된 149 염기쌍을 시작으로 151, 153, 155, 157, 159, 161, 163 염기쌍의 형태를 보였다. 정신분열병 환자군과 정상대조군간에 도형접합체 및 이형접합체 빈도의 유의한 차이는 없었다. 환자군과 정상대조군의 대립유전자 분포의 빈도는 통계적으로 유의한 차이가 없었다. 더욱이 각각의 대립유전자 분포에서도 양군간 유의한 차이는 없었다. 또한 동질의 아형으로 분류해 보기위해 임상아형, 양성 및 음성증상군, 가족력의 유무에 따라 비교적 동질적인 표현형을 가진 집단으로 나눈 후 대립유전자 분포를 비교해 보았으나 통계적으로 유의한 차이를 보이지 않았다. 결 론 : 본 연구에서는 Interleukin-2 수용체 β chain 유전자가 정신분열병의 병인론에 관련된다는 가설을 지지할 만한 긍정적 소견을 얻지 못했다. Background : While a significant genetic predisposition to schizophrenia has been proposed, the mode of inheritance or nature of etiological factors is unknown. Previous reports of a genome-wide survey for schizophrenia susceptibility genes have indicated a possible region of linkage on chromosome 22. In order to test the possibility that the interleukin-2 receptor β chain(IL-2Rβ) gene on chromosome 22 is of etiological importance in schizophrenia, a case-control association study was conducted. Methods : Subjects were ninety-three schizophrenic patients with a diagnosis of schizophrenia by DSM-Ⅲ-R criteria and ninety-seven normal controls, Schizophrenic patients were divided by clinical phenotypes such as DSM-Ⅲ-R diagnostic subtypes, positive and negative symptoms, and family history so as to increase the homogeneity of schizophrenics. Genomic DNA was extracted from whole blood lymphocytes according to standard procedures. The DNA was used to study a dinucleotide repeat in the IL-2Rβ gene. To reveal the dinucleotide polymorphism. genomic DNA of subjects was amplified by polymerase chain reactions(PCR). Results : At the IL-2Rβ gene locus, all the previously reported alleles(eight different alleles) of a dinucleotide polymorphism were identified. There was no significant difference between number of heterozygosity in schizophrenic patients and in normal controls. There was no significant difference in the distribution of frequencies of alleles between schizophrenics and normal controls. In addition, there was no significant difference in the allele frequencies among subtypes of schizophrenic patients according to DSM-Ⅲ-R diagnostic subtypes, positive and negative symptoms, and family history. Conclusion : The present study did not detect a difference in frequencies of alleles of a dinucleotide polymorphism at the IL-2Rβ gene locus between schizophrenic patients and normal controls. These results do not supports an evidence that IL-2Rβ gene plays, a major role in the etiology of schizophrenia.

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>

금은화(金銀花) 및 금은화전초(金銀花全草)가 Raw 264.7 cell에서 LPS로 유도된 NO의 생성, iNOS, COX-2 및 cytokine에 미치는 영향

이동언,이재령,김영우,권영규,변성희,신상우,서성일,권택규,변준석,김상찬,Lee, Dong-Eun,Lee, Jae-Ryung,Kim, Young-Woo,Kwon, Young-Kyu,Byun, Sung-Hui,Shin, Sang-Woo,Suh, Seong-Il,Kwon, Taeg-Kyu,Byun, Joon-Seok,Kim, Sang-Chan 대한동의생리학회 2005 동의생리병리학회지 Vol.19 No.2

Lonicerae Flos has antibacterial effects against Staphylococcus aureus, streptococci, pneumococci, Bacillus dysenterii, Salmonella typhi, and paratyphoid. It is an antiviral agent. The herb has a cytoprotective effect against $CCl_{4}-induced$ hepatic injury. It has antilipemic action, interfering with lipid absorption from the gut. Nowadays this herb is used mainly in the treatment of upper respiratory infections, such as tonsillitis and acute laryngitis. It is also used in the treatment of skin suppurations, such as carbuncles, and to treat viral conjunctivitis, influenza, pneumonia, and mastitis. Lonicerae Flos is dried flower buds of Lonicera japonica, L. hypoglauca, L. confusa, or L. dasystyla. But, for the most part, we use whole plant of Lonicera japonica, as a flower bud of it. And, little is known of the original copy of effects of whole plant, except for the 'Bon-Cho-Gang-Mok', which is written the effects of flower of Lonicera japonica are equal to effects of leaves and branch of it. The present study was conducted to evaluate the effect of flower and whole plant of Lonicera japonica on the regulatory mechanism of cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, flower and whole plant of Lonicera japonica water extracts inhibited nitric oxide production in a dose-dependent manner and abrogated iNOS and COX-2. Flower and whole plant of Lonicera japonica water extract did not affect on cell viability. To investigate the mechanism by which flower and whole plant of Lonicera japonica water extract inhibits iNOS and COX-2 gene expression, we examined the on phosphorylation of inhibitor ${\kappa}B{\alpha}$ and assessed production of $TNF-{\alpha}$, $interleukin-1{\beta}$ $(IL-1{\beta})$ and interleukin-6 (IL-6). Results provided evidence that flower and whole plant of Lonicera japonica inhibited the production of $IL-1{\beta}$, IL-6 and activated the phosphorylation of inhibitor ${\kappa}B{\alpha}$ in Raw 264.7 cells activated with LPS. These findings suggest that flower and whole plant of Lonicera japonica can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections, respectively.

Comparison of inflammatory markers for the prediction of neointimal hyperplasia after drug-eluting stent implantation

Kang, Woong Chol,Il Moon, Chan,Lee, Kyounghoon,Han, Seung Hwan,Suh, Soon Yong,Moon, Jeonggeun,Shin, Mi Seung,Ahn, Taehoon,Shin, Eak Kyun Lippincott Williams Wilkins, Inc. 2011 Coronary artery disease Vol.22 No.8

BACKGROUND: We compared the relationship between inflammatory markers and neointimal hyperplasia (NIH) after drug-eluting stent (DES) implantation. METHODS: We implanted a single DES in 42 consecutive patients with stable angina. The plasma high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) levels were measured before, and 24 and 72 h after the procedure. Angiography and intravascular ultrasound were performed. RESULTS: No relationship was noted between the baseline hs-CRP level and NIH. A significant positive correlation was noted between NIH and the hs-CRP level obtained at 24 h (r=0.435, P=0.004), and 72 h (r=0.334, P=0.031) after the procedure. Interestingly, there was a positive correlation between the change (&Dgr;) in the hs-CRP level and NIH at 24 h (r=0.414, P=0.006). The fourth quartile of the hs-CRP at 24 h after percutaneous coronary intervention (PCI) had significantly larger volume of NIH than the first quartile (20.1±25.1 vs. 2.7±6.4 mm, P<0.05). Moreover, NIH in the fourth quartile (20.9±26.4 mm) was higher than the first quartile (3.3±8.6 mm) of the &Dgr; hs-CRP level at 24 h (P<0.05) after the procedure. Although the IL-6 level at the baseline and 72 h after the procedure were positively correlated with NIH (r=0.337, P=0.029 and r=0.435, P=0.004, respectively), the &Dgr; IL-6 level at any stage was not correlated with NIH. Neither the MMP-9 level nor the &Dgr; MMP-9 level at any stage was correlated with NIH. CONCLUSION: This prospective intravascular ultrasound study showed the inflammatory response after PCI, as measured by hs-CRP levels, but not the baseline hs-CRP level, predict NIH after DES implantation. Neither a change in the IL-6 nor MMP-9 levels at any stage after PCI reflected NIH.

Therapeutic effect of a novel histone deacetylase 6 inhibitor, CKD-L, on collagen-induced arthritis in vivo and regulatory T cells in rheumatoid arthritis in vitro

Oh, Bo Ram,Suh, Dong-hyeon,Bae, Daekwon,Ha, Nina,Choi, Young Il,Yoo, Hyun Jung,Park, Jin Kyun,Lee, Eun Young,Lee, Eun Bong,Song, Yeong Wook BioMed Central 2017 Arthritis research & therapy Vol.19 No.-

<P><B>Background</B></P><P>Histone deacetylase (HDAC) inhibitor has recently been reported to have a therapeutic effect as an anti-inflammatory agent in collagen-induced arthritis (CIA). We investigated the therapeutic effect of a new selective HDAC6 inhibitor, CKD-L, compared to ITF 2357 or Tubastatin A on CIA and regulatory T (Treg) cells in patients with rheumatoid arthritis (RA).</P><P><B>Methods</B></P><P>CIA was induced by bovine type II collagen (CII) in DBA/1 J mice. Mice were treated with HDAC inhibitor for 18 days. Arthritis score was assessed and histological analysis was performed by hematoxylin and eosin (H&E) stain. Cytotoxic T-lymphocyte associated protein (CTLA)-4 expression in induced Treg cells was analyzed and suppression assay was analyzed using Treg cells and effector T (Teff) cells isolated from naive C57BL/6 mice by flow cytometry. Cytokines were analyzed in peripheral blood mononuclear cells (PBMC) of five patients with RA by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Tumor necrosis factor (TNF) was analyzed using PMA- activated THP-1 cells by ELISA. Suppression assay was analyzed using Treg cells and Teff cells isolated from RA patients by flow cytometry.</P><P><B>Results</B></P><P>In the CIA model, CKD-L and Tubastatin A significantly decreased the arthritis score. CKD-L increased CTLA-4 expression in Foxp3<SUP>+</SUP> T cells and inhibited the proliferation of Teff cells in the suppression assay. In RA PBMC, CKD-L significantly inhibited TNF and interleukin (IL)-1β, and increased IL-10. CKD-L and Tubastatin A inhibited TNF secretion from PMA-activated THP-1 cells. CKD-L and ITF 2357 inhibited the proliferation of Teff cells in RA patients in the suppression assay. Tubastatin A had no effect on inhibition of proliferation.</P><P><B>Conclusion</B></P><P>CKD-L decreased the arthritis score in CIA, reduced the expression of TNF and IL-1β, and increased the expression of IL-10 in PBMC from RA patients. CKD-L increased CTLA-4 expression and the suppressive function of Treg cells. These results suggest that CKD-L may have a beneficial effect in the treatment of RA.</P>

흰쥐의 좌골신경 절단 후 요추척수에서 소교세포의 증식과 소멸에 따른 Cytokine의 발현

김상표,서성일,조영록,조승제,김승필,박종욱,곽정식,박종욱 대한병리학회 1998 Journal of Pathology and Translational Medicine Vol.32 No.2

Inhibitory Effect of Farfarae Flos Water Extract on COX-2, iNOS Expression and Nitric Oxide Production in lipopolysaccharide - activated RAW 264.7 cells

Yoon Tae Gyoung,Byun Boo Hyeong,Kwon Teag Kyu,Suh Seong Il,Byun Sung Hui,Kwon Young Kyu,Kim Sang Chan The Physiological Society of Korean Medicine and T 2004 동의생리병리학회지 Vol.18 No.3

Farfrae Flos has been clinically used for the treatment of asthma in traditional oriental medicine. There is lack of studies regarding the effects of Farfrae Flos on the immunological activities. The present study was conducted to evaluate the effect of Farfrae Flos on the regulatory mechanism of cytokines and nitric oxide (NO) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, Farfrae Flos water extract inhibited nitric oxide production in a dose-dependent manner and abrogated inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Farfrae Flos water extract did not affect on cell viability. To investigate the mechanism by which Farfrae Flos water extract inhibits iNOS and COX-2 gene expression, we examined the on the phospholylation of inhibitor κBα and production of TNF-α, IL-1β and IL-6. Results provided evidence that Farfrae Flos inhibited the production of interleukin-1β (IL-1β) and the activation of phospholylation of inhibitor κBα in Raw 264.7 cells activated with LPS. These findings suggest that Farfrae Flos can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

고온 환경에서의 운동 시 서로 다른 수분 보충이 엘리트 운동선수들의 염증성 사이토카인 반응 및 면역 기능에 미치는 영향

백일영 ( Il Young Paik ),윤두상 ( Doo Sang Yun ),서상훈 ( Sang Hoon Suh ),노희태 ( Hee Tae Roh ) 한국스포츠정책과학원(구 한국스포츠개발원) 2011 체육과학연구 Vol.22 No.3

이 연구의 목적은 고온 환경에서의 운동 시 단순 수분 및 스포츠 음료를 통한 수분 보충이 엘리트 운동선수들의 호르몬 변화, 염증성 사이토카인 반응 및 면역 기능에 미치는 영향을 규명하는데 있다. 연구의 대상은 엘리트 운동선수 10명으로 하였으며, 4가지 실험 처치 조건에서 75%HRR 운동 강도로 60분간 트레드밀 달리기를 실시하였다: 1) 적정 환경에서 운동 처치 조건(TE), 2) 고온 환경에서 운동 처치 조건(HE), 3) 고온환경에서 운동 시 물 섭취 처치 조건(HW), 4) 고온 환경에서 운동 시 스포츠음료 섭취 처치 조건(HS). 기후조건은 인공기후실을 이용하여 적정 환경은 온도 18℃, 상대습도 50%로 설정하였으며, 고온 환경은 온도 32℃, 상대습도 50%로 설정하였다. 수분 보충은 물 또는 스포츠음료를 이용하여 고온 환경에서 운동 처치 조건(HE)의 운동 전, 후 체중 차와 동일한 양을 구강 투여하였다. 채혈은 안정 시, 운동 직후, 회복 60분 시점에서 실시하였다. 연구결과, 운동 직후 시점에서 epinephrine은 HE 처치가 다른 세 처치(TE, HW, HS)보다 유의하게 높았으며(p<.05), norepinephrine은 HE 처치가 TE 처치보다 유의하게 높았다(p<.05). IL-6는 운동 직후 시점에서 HE 처치가 TE 처치보다 유의하게 높았다(p<.05). TNF-α는 TE 처치를 제외한 세 처치(HE, HW, HS)에서 운동 직후 유의하게 증가하였다(p<.05). T-cell은 TE 처치를 제외한 세 처치(HE, HW, HS)에서 운동 직후 유의하게 증가하였으며(p<.05), HE 처치가 TE 처치보다 유의하게 높았다(p<.05). NK-cell은 운동 직후 시점에서 HE 처치가 TE 처치보다 유의하게 높았다(p<.05). Neutrophil은 HE 처치의 경우 운동 직후 시점에서 유의하게 증가하였다(p<.05). Lymphocyte는 TE와 HE 처치에서 운동 직후 유의하게 증가하였다(p<.05). Monocyte는 운동 직후 시점에서 HE 처치가 TE 처치보다 유의하게 높았다(p<.05). 이상의 결과를 종합하면, 고온 환경에서의 운동은 적정 환경에서의 운동 시보다 카테콜아민과 염증성 사이토카인의 분비를 증가시켜 면역기능에 부정적인 영향을 미칠 수 있는 것으로 나타났다. 반면에 고온 환경에서의 운동 시 수분 보충은 탈수와 열적 스트레스를 경감시켜 면역기능의 부정적 영향을 완화시킬 수 있음을 시사한다. The purpose of the current research was to investigate the effects of body fluid replacement by water or sport drinks on the hormonal, inflammatory cytokine and immune responses during exercise in high ambient temperature. The subjects of the current research were 10 elite athletes. The subjects were asked to perform treadmill running at 75%HRR for 60 minutes in four different conditions, controlled by the environmental chamber: 1) thermoneutral environment (TE), 2) high ambient temperature environment (HE), 3) high ambient temperature environment and body fluid replacement by water (HW), and 4) high ambient temperature environment and body fluid replacement by sport drink(HS). Ambient temperature and relative humidity were set at 18℃ and 50%, respectively, for the theromoneutral environment, and 32℃ and 50% for the high ambient temperature environment. The amount of fluid replaced during two different fluid replacing conditions (HW and HS) were equivalent to the difference in body weight between pre and post completion of the running in HE. The defined amounts of the fluids were administered orally with separations during the exercise trials. Blood samples were taken at rest, at immediately after exercise, and at 60-minute of recovery. For catecholamine responses, the level of epinephrine immediately after exercise appeared to be significantly higher in HE compared to the other treatment conditions (p<.05), while the level of norepinephrine appeared to be significantly higher in HE compared to TE (p<.05). For cytokine responses, the level of IL-6 immediately after exercise appeared to be significantly higher in HE compared to TE (p<.05) while the levels of TNF-α were shown to significantly increase at immediately after exercise in all treatment conditions except TE (p<.05). For immune responses, the levels of T-cell were shown to significantly increase at immediately after exercise in all treatment conditions except TE (p<.05), and the level appeared to be significantly higher in HE compared to TE (p<.05); the level of NK-cell appeared to be higher at immediately after exercise in HE compare to TE (p<.05); the level of neutrophil was shown to significantly increase at immediately after exercise in HE (p<.05); the levels of lymphocyte were shown to significantly increase in TE and HE at immediately after exercise (p<.05); and the level of monocyte appeared to be significantly higher in HE compared to TE at immediately after exercise (p<.05). On the base of the results of the current study, it is suggested that exercise in high ambient temperature can induce increase responses of catecholamines and cytokines which may negatively influence on immune functions. Body fluid replacements during exercise in high ambient temperature, however, can attenuate the negative consequences of thermal stress on immune functions by preventing dehydration and reducing thermal stress.