표재성방광암 환자에서 Intravesical BCG Therapy후 Cytokines 변화

김상완,김달식,김형진 大韓泌尿器科學會 1999 Korean Journal of Urology Vol.40 No.1

진주종 조직에서 골파괴와 연관된 Cytokine 유전자 발현

박철원,장영호,유연희,안명주 대한이비인후과학회 1999 대한이비인후과학회지 두경부외과학 Vol.42 No.2

The Effect of Abdominal Visceral Fat, Circulating Inflammatory Cytokines, and Leptin Levels on Reflux Esophagitis

( Su Youn Nam ),( Il Ju Choi ),( Kum Hei Ryu ),( Bum Joon Park ),( Young Woo Kim ),( Hyun Beom Kim ),( Jeongseon Kim ) 대한소화기기능성질환·운동학회 2015 Journal of Neurogastroenterology and Motility (JNM Vol.21 No.2

Background/Aims Although adipocytes secrete inflammatory cytokines and adipokines, their role in reflux esophagitis is controversial. We investigated the association between visceral fat and inflammatory cytokines or adipokines in reflux esophagitis. Methods Abdominal visceral fat and cytokines were measured in 66 individuals with reflux esophagitis and 66 age- and sex-matched controls. The mean values for visceral fat and cytokines were compared in cases and controls. Second, correlations between visceral fat and inflammatory cytokines were measured. Finally, multiple logistic regression models for odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the effects of visceral fat and cytokines on reflux esophagitis. Results Visceral fat, leptin, interleukin (IL)-6, and IL-1β were higher in reflux esophagitis compared to controls. Visceral fat showed a strong positive correlation with IL-6 (r = 0.523, P < 0.001), IL-8 (r = 0.395, P < 0.001), and IL-1β (r = 0.557, P < 0.001), and a negative correlation with adiponectin (r = -0.466, P < 0.001). With adjusted analysis, visceral fat/100 (OR, 4.32; 95% CI, 2.18-8.58; P < 0.001) and leptin (OR, 1.36; 95% CI, 1.10-1.69; P = 0.005) independently increased the risk of reflux esophagitis, but the effects of other cytokines were abolished. Conclusions Visceral fat may increase the risk of reflux esophagitis by increasing the levels of inflammatory cytokines. Leptin showed a positive association with reflux esophagitis that was independent of visceral fat. (J Neurogastroenterol Motil 2015;21:247-254)

호중구 감소가 동반된 환자에서 발열에 따른 혈청내 IL-β, IL-6, TNF-α의 상승과 C-reactive protein과의 연관성

최정현,김유진,권혁상,김영환,정정조,유진홍,김양리,신완식,강문원 대한화학요법학회 1996 대한화학요법학회지 Vol.14 No.1

저자들은 1995년 3월에서 1995년 10월까지 성모병원에 입원한 급성 백혈병, 골수이형성증환자 중 항암제 치료나 기저질환으로 호중구가 감소된 상태에서 발열이 있었던 환자에서 발열을 전후로 하여 IL-1β, IL-6, TNF-α와 CRP의 상승정도를 측정, 비교하여 다음과 같은 결과를 얻었다. 1. IL-1β는 발열전 78.7±31.0 pg/ml에서 발열 후 120.6±88.8 pg/ml로 상승하였으나 통계학적 유의성은 없었다 (p=0.054). 그러나 IL-6의 경우 285.5±157.9 pg/ml에서 468.2±247.4 pg/ml로 증가하였고(p<0.01), TNF-α는 223.1±111.7 pg/ml에서 544.9±207.1 pg/ml로 증가하여(p<0.01)로 발열전에 비하여 통계학적으로 유의한 증가를 관찰할 수 있었다. 또한 CRP의 경우도 발열전 7.67±7.1 mg/L에서 발열후 126.8±37.1 mg/L로 증가하여 통계학적으로 유의한 상승을 보였다(p<0.01). 2. CRP의 상승 정도와 IL-1β, IL-6 그리고 TNF-α와 같이 발열에 관여하는 cytokine의 상승과의 연관관계는 관찰할 수 없었다. 3. 감염의 형태에 따른 CRP 및 IL-1β, IL-6, TNF-α와 같은 cytokine의 유의한 차이는 관찰할 수 없었다. 4. IL-6, TNF-α는 발열이 시작되면서 급속히 상승된후 상승된 수치가 유지되는 양상을 보였으나 IL-1β는 발열 2일째 까지 지속적으로 상승한 후 바로 떨어지기 시작하여 발열 3일째는 발열전과 유사한 농도까지 감소하는 것이 관찰되었다. CRP는 발열 후 급속히 상승하여 발열기간동안 지속적으로 상승되어 있는 경향을 보였다. 이상의 결과로 보아 현재 흔히 임상적으로 감염성 질환의 지표로 사용되고 있는 CRP는 패혈증과 패혈성 속을 매개하는 가장 중요한 cytokine인 IL-1β, IL-6, 그리고 TNF-α의 상승과 지속에 유사한 pattern으로 상승, 유지되어 감염의 진행정도를 파악하는데 있어 유용하다고 판단하였다. 그러나 CRP의 상승정도와 cytokine의 상승정도의 연관성은 없었으며 CRP와 cytokine의 상승정도로 감염의 형태, 예후등을 판정하기는 어려울 것으로 추정된다. 추후 더 많은 수의 환자를 장기간 추적 관찰하고 cytokine mRNA를 정량적으로 분석하는 방법을 병합한 정밀한 연구가 필요할 것으로 사료된다. Cytokiness, especially interleukin 1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNT-α) play a important role in the genesis and progression of the sepsis and septic shock. We monitored these three cytokines in 16 netropenic patients before and after the onset of febrile episode. Serum levels of IL-6 and TLF-α was significantly increased after onset of fever(p<0.01). IL-1β was also increased, but it was insignificant statistically(p=0.054). But the measurement of these cytokines has difficulties in clinical application in many aspects. So we also monitored CRP which is known as an acute phase reactant protein produced by IL-6 in the liver and clinically available with ease. CRP was also increased significantly after the fever(p<0.01). But its increase had no relationship with the increase of these cytokines. There was no difference in the extent of increment of these cytokines and CRP by the type of infection, too. But the kinetic patterns of the CRP and these cytokines was very similar. We conclude that CRP is a useful marker of infection and reflects the infectious process, but CRP as well as cytokines are not a useful predictor of the prognosis or the infectious etiology. In future, lager clinical trials and quantitative analysis of cytokine mRNA are needed.

Balb/C mouse의 폐장대식세포에서 유리규산 자극에 의한 Proinflammatory Cytokine과 TGF-$\beta$의 생성 및 상관관계

기신영,김은영,김미호,어수택,김용훈,박춘식,이희발,Ki, Shin-Young,Kim, Eun-Young,Kim, Mi-Ho,Uh, Soo-Taek,Kim, Yong-Hoon,Park, Choon-Sik,Lee, Hi-Bal 대한결핵및호흡기학회 1998 Tuberculosis and Respiratory Diseases Vol.45 No.4

연구배경: 유리규산(silica) 자극에 의해 폐장내 대식세포에서 형성되는 proinflammatory cytokines인 IL-1$\beta$, IL-6, TNF-$\alpha$와 fibrogenic cytokine인 TGF-$\beta$, PDGF는 섬유화 과정에 매우 중요한 역할을 한다. 그러나 이러한 cytokine 의 역할과 상호관련성에 대해서는 아직 확실히 밝혀진 바없다. 본 연구는 Balb/C mouse의 폐장단구세포를 silica로 자극시 형성되는 IL-6, TNF-$\alpha$ 폐섬유화의 발생과 유지에 중요한 역할을 할 것으로 기대되는 TGF-$\beta$ 의 생성을 관찰하고 TGF-$\beta$의 생성에 proinflammatory cytokine이 미치는 영향에 대해서 알아보고자 하였다. 방 법: Balb/C 의 폐장대식세포를 silica로 자극한 후 IL-6, TNF-$\alpha$ TGF-$\beta$의 양을 bioassay로 측정하였고 mRNA의 발현을 in situ hybridization을 통해 관찰하였으며, 대식세포의 TGF-$\beta$ 생성에 대한 IL-1$\beta$, IL-6, TNF-$\alpha$의 영향을 알기 위하여 L-1, IL-6, TNF-$\alpha$에 대한 중화항체를 이용하여 대식세포의 TGF-$\beta$의 생성 억제 유, 무를 관찰하였다. 결 과: Silica로 대식세포자극시 TNF-$\alpha$는 초기 4 시간째 최고의 생성능을 보였으며, IL-6 는 silica 0.2 ${\mu}g/ml$의 농도에서 배양 8 시간째 생성능이 가장 높았고 배양 12 시간째는 다시 감소하였다가 24시간째 증가하는 biphasic한 소견을 보여 주었다. TGF-$\beta$는 silica의 양과 관계없이 배양 24시간째 자연생성능뿐 아니라, silica로 자극시에도 증가되었다. Silica와 TNF-$\alpha$ 50ng/ml을 함께 자극시 TGF-$\beta$의 생성은 현저히 증가되었으며, TNF-$\alpha$ 50 ng/ml과 IL-6 50 ng/ml으로 동시 자극시에는 TNF-$\alpha$에 의한 TGF-$\beta$의 형성이 증가하는 경향을 보였다. TNF-$\alpha$의 중화항체를 전처치 후 silica 자극시 TGF-$\beta$의 생성능을 억제시킴을 관찰할 수 있었다. Anti-IL-$\beta$, anti-IL-6, anti-TNF-$\alpha$ antibody 모두를 통시에 투여하였을 때도 silica에 의한 TGF-$\beta$의 생성능을 억제시킴을 관찰할 수 있었다. Silica 자극 후 대식세포의 in situ hybridization에서 TNF-$\alpha$ mRNA는 2시간째부터 발현되었고 IL-6 mRNA는 4 시간째부터 발현된 후 8 시간째 소실되었고 TGF-mRNA는 12 시간째 가장 강한 발현을 보였다. 결 론: Silica 자극에 의해 폐장대식세포는 자극 초기에는 TNF-$\alpha$가 가장먼저 형성되고 후기에 TGF-$\beta$가 형성되며 TNF-$\alpha$가 TGF-$\beta$ 형성에 중요한 역할을 할 것으로 사료되었다. Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

Regulation of Osteoclast Differentiation by Cytokine Networks

Dulshara Sachini Amarasekara,윤형석,김수미,이나리,김현종,노재랑 대한면역학회 2018 Immune Network Vol.18 No.1

Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.

건선 병변부 및 병변주위부 피부의 Cytokines 유전자 발현

윤기성,김도원,정상립,김문규,김정철 경북대학교 병원 1997 경북대학교병원의학연구소논문집 Vol.1 No.1

It has been proposed that cytokines may be involved in mediating the characteristic pathological changes in psoriasis, including epidermal hyperplasia, compromised keratinocyte differentiation, and dermal and epidermal infiltration by polymorphonuclear leukocytes and mononuclear cells. The purpose of this study os to assess the pattern of cytokine gene expression in psoriatic skin lesion. To investigate the cytokine expression pattern, we examined the transcripts of cytokine genes using reverse transcription and polymerase chain reaction (RT-PCR) method with 13 cytokine-specific primers. The Results were as follow; 1. Only the TGF-β gene was expressed in the normal skin. 2. IL-1α, IL-1β, IL-8, and TGF-β were detected in both lesional and perilesional psoriatic skin. The lesions showed more prominent expression. 3. IL-10 and GM-CSF were weakly detectable in three lesional psoriatic skin respectively, and IL-2R in two lesional psoriatic skin. 4. IL-2,IL-4,IL-5,IL-6 TNF-α, IFN-γ were not detectable on both lesional and perilesional psoriatic skin. Therefore, distinct differences in the cytokines gene expression were noted between normal and psoriatic skin. The patterns of cytokines gene expression in perilesional skin were similiar to those of lesional psoriatic skin.

Transduced Tat-DJ-1 protein inhibits cytokines-induced pancreatic RINm5F cell death

( Hyo Sang Jo ),( Hyeon Ji Yeo ),( Hyun Ju Cha ),( Sang Jin Kim ),( Su Bin Cho ),( Jung Hwan Park ),( Chi Hern Lee ),( Eun Ji Yeo ),( Yeon Joo Choi ),( Won Sik Eum ),( Soo Young Choi ) 생화학분자생물학회(구 한국생화학분자생물학회) 2016 BMB Reports Vol.49 No.6

Loss of pancreatic β-cells by oxidative stress or cytokines is associated with diabetes mellitus (DM). DJ-1 is known to as a multifunctional protein, which plays an important role in cell survival. We prepared cell permeable wild type (WT) and mutant type (M26I) Tat-DJ-1 proteins to investigate the effects of DJ-1 against combined cytokines (IL-1β, IFN-Υ and TNF-α)-induced RINm5F cell death. Both Tat-DJ-1 proteins were transduced into RINm5F cells. WT Tat-DJ-1 proteins significantly protected against cell death from cytokines by reducing intracellular toxicities. Also, WT Tat-DJ-1 proteins markedly regulated cytokines-induced pro- and anti-apoptosis proteins. However, M26I Tat-DJ-1 protein showed relatively low protective effects, as compared to WT Tat-DJ-1 protein. Our experiments demonstrated that WT Tat-DJ-1 protein protects against cytokine-induced RINm5F cell death by suppressing intracellular toxicities and regulating apoptosisrelated protein expression. Thus, WT Tat-DJ-1 protein could potentially serve as a therapeutic agent for DM and cytokine related diseases. [BMB Reports 2016; 49(5): 297-302]

인류의 신장 혈관간세포에서 유착분자 발현과 Chemokine 발현에 미치는 Th1 Cytokine과 Th2 Cytokine의 상호 작용

나경선 ( Kyoung Sun Na ),강태영 ( Tae Young Kang ),이진숙 ( Jin Sook Lee ),박용욱 ( Yong Wook Park ),이혜순 ( Hye Soon Lee ),엄완식 ( Wan Sik Uhm ),김태환 ( Tae Hwan Kim ),전재범 ( Jae Bum Jun ),배상철 ( Sang Cheol Bae ),이춘용 ( 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.2

Purpose: Predominance of IFN-γ over Th2 cytokines is evident in proliferative lupus nephritis. Th2 cytokines such as IL-10, or IL-4 have been known to suppress Th1 cytokine driven pro-inflammatory responses. However a combination of cytokines can exert variable effects during the evolution of autoimmune diseases depending on the various factors, such as the stage of diseases or local versus systemic expression. To determine whether Th2 cytokines play a pro- or anti-inflammatory role in the local glomerular inflammation induced by IFN-γ, we studied the effect of IL-10 and IL-4 on the expression of chemokines and adhesion molecules in human mesangial cells stimulated with IFN-γ. Methods: Human mesangial cells were obtained from 3 patients undergoing nephrectomy. MCP-1, RANTES, ICAM-1, and CD40 expressions were examined in response to various cytokine stimulation; IFN-γ, IL-10, IL-4, IFN-γ+IL-10, IFN-γ+IL-4, and IFN-γ+IL-10+IL-4, respectively. Expression of MCP-1 mRNA was analyzed by RT-PCR and the levels of MCP-1 and RANTES in the culture supernatants were measured using an enzyme immunoassay. ICAM-1 and CD40 surface expressions were analyzed by flow cytometry. Results: IFN-γ increased basal mRNA expression of MCP-1, and IL-10 strongly enhanced the level of MCP-1 mRNA and protein expressions induced by IFN-γ. IL-4 did not affect significantly on the MCP-1 expression induced by IFN-γ. Although IFN-γ increased the concentration of RANTES, IL-10 and IL-4 did not affect IFN-γ induced RNTES expression. Increased expression of ICAM-1 and CD40 induced by IFN-γ were not down-regulated by IL-10 or IL-4. Conclusion: Taken together, IL-10 appears to augment local inflammatory reaction though the up-regulation of MCP-1 from mesangial cells in the presence of IFN-γ rather than inhibit inflammatory response in the pathogenesis of proliferative glomerulonephritis.

Regulation of Osteoclast Differentiation by Cytokine Networks

Amarasekara, Dulshara Sachini,Yun, Hyeongseok,Kim, Sumi,Lee, Nari,Kim, Hyunjong,Rho, Jaerang 한국조명·전기설비학회 2018 한국조명·전기설비학회 학술대회논문집 Vol. No.

<P>Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.</P>