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Neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment via the HMGB1/RAGE/il-8 axis

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Cancer Biology & Medicine 2020年第1期17卷 154-168页

作者： Caijun Zha Xiangqi Meng Lulu Li Shan Mi Da Qian Ziwei Li Pengfei Wu Shaoshan Hu Shihong Zhao Jinquan Cai Yanhong Liu Department of Laboratory Diagnosis The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China Department of Neurosurgery The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China Neuroscience Institute Heilongjiang Academy of Medical SciencesHarbin 150086China

Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of ***,the mechanisms underlying the involvement of NETs in glioma progression remain largely *** study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor ***:Neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry,and their relationships with clinicopathological features and outcomes were statistically *** effects of NETs on glioma cell progression were studied in a co-culture *** vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs,as well as the ERK signaling pathway activation and the metastasis of ***:Neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade *** induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and *** overproduction promoted glioma cell proliferation,migration,and ***,HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in *** addition,NETs stimulated the NF-κB signaling pathway,thus promoting il-8 secretion in ***,il-8 recruited neutrophils which in turn mediated NETs formation via the PI3 K/AKT/ROS axis in ***:Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/il-8 *** NETs formation or il-8 secretion may be an effective approach to inhibit glioma progression.

关键词： Neutrophil extracellular traps HMGB1 il-8 NF-κB glioma microenvironment

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Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/il-8 signaling pathway

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2835-2849页

作者： Yumiao Zhao Jiaxin Sun Yin Li Xiuman Zhou Wenjie Zhai Yahong Wu Guanyu Chen Shanshan Gou Xinghua Sui Wenshan Zhao Lu Qiu Yongjie Yao Yixuan Sun Chunxia Chen Yuanming Qi Yanfeng Gao School of Life Sciences Zhengzhou UniversityZhengzhou 450001China Thoracic Surgery Department National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China School of Pharmaceutical Sciences(Shenzhen) Sun Yat-sen UniversityShenzhen 518107China

Tryptophan 2,3-dioxygnease 2(TDO2) is specific for metabolizing tryptophan to kynurenine(KYN),which plays a critical role in mediating immune escape of *** accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers,its tumor-promoting role in esophageal squamous cell carcinoma(ESCC) remains ***,we observed that TDO2 was overexpressed in ESCC tis sues and correlated significantly with lymph node metastasis,advanced clinical stage,and unfavorable *** experiments showed that TDO2 promoted tumor cell proliferation,migration,and colony formation,which could be prevented by inhibition of TDO2 and aryl hydrocarb on receptor(AHR).Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model,tumor burden of C57 BL/6 mice with ESCC induced by 4-NQO,enhance the expression of phosphorylated AKT,with subsequent pho sphorylation of GSK3β,and polarization of M2 macrophages by upregulating interleukin-8(il-8) to accelerate tumor progression in the tumor microenvironment(TME).Collectively,our results discovered that TDO2 could upregulate il-8 through AKT/GSK3β to direct the polarization of M2 macrophages in ESCC,and suggested that TDO2 could represent as an attractive therapeutic target and prognostic marker to ESCC.

关键词： Tryptophan 2,3-dioxygenase 2 M2 macrophage Esophageal squamous cell carcinoma il-8 KYN

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Regulatory Effect of E2,il-6 and il-8 on the Growth of Epithelial Ovarian Cancer Cells

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Cellular & Molecular Immunology 2005年第5期2卷 365-372页

作者： Yue Wang Jie Yang Yan Gao Yongrui Du Leyuan Bao Wenyan Niu Zhi Yao Department of Immunology Tianjin Medical University Tianjin 300070 China Department of Gynecologic Oncology Tianjin Women＇s Hospital Tianjin 300070 China Corresponding to： Dr. Zhi Yao Department of Immunology Tianjin Medical University 22 Qixiangtai Road Tianjin 300070 China

To determine the regulatory effects of estrogen and cytokine il-6 and il-8 on the growth of epithelial ovarian cancer （OVCA）, we first examined the status of estrogen receptors （ERα and ERβ）, il-6 receptor （il-6Rα and gp130）, and il-8 receptor （il-8RA and il-8RB） on five epithelial OVCA cell lines by semiquantitative RT-PCR and Western blot analysis. Results showed that the expressions of these receptors were variable on the five cells. Those OVCA ceUs expressing the receptors were selected to study related molecular mechanism. MTT assay was performed to observe the effects of 17β-estradiol （E2）, il-6 and il-8 on cell proliferation. We discovered that E2 markedly promoted the proliferation of CAOV-3 and OVCAR-3 cell in a time- and dose-dependent manner. Tamoxifen （Txf）, an ER inhibitor, completely blocked the proliferation of the E2-induced cells, and il-6- or/and il-8-neutralizing antibody only showed partially blocking activity. il-6 and il-8 were able to significantly stimulate CAOV-3 and OVCAR-3 cell proliferation in a time- and dose-dependent manner, which had a potential synergistic effect on CAOV-3 cells but not on OVCAR-3 cells. The cell proliferation induced by these two cytokines was abolished completely by their specific neutralizing antibodies, partially by Txf, but not by unrelated goat IgG. Taken together, our results suggested that estrogen, il-6 and il-8 could modulate OVCA growth by forming a reciprocal cascade with amplifying effect.

关键词： estrogen il-6 il-8 cell proliferation epithelial ovarian cancer

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Role of mechanical stretching and lipopolysaccharide in early apoptosis and il-8 of alveolar epithelial typeⅡcells A549

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Asian Pacific Journal of Tropical Medicine 2012年第8期5卷 638-644页

作者： Qiao-Ming Ning Xiao-Ning Sun Xin-Kai Zhao Department of Anesthesiology Hainan Provincial Hospital

Objective:To investigate the effects of mechanical stretching and lipopolysaccharide(LPS) on the early apoptosis and il-8 production of alveolar epithelial type II cells ***:The experimental matrix consisted of three integrated *** the first study,A549 cells were subjected to different stretching strain frequency and duration time to see the effects on the early *** the second study,A549 cells were subjected to mechanical stretch(13%4 h, 0.3 Hz) and LPS(1 or 100 ng/mL) to see whether mechanical strain and LPS also have an addictive effect on the early *** the third study to investigate whether this addictive effect could be induced by LPS and mechanical stretch on il-8 production,A549 cells were subjected to LPS(100 ng/mL) and mechanical strain(13%.0.3 Hz,4 h).Real time PCR and enzyme linked immunosorbent assay were used to measure mRN A and protein level of *** early apoptosis was detected by flow ***:Mechanical stretch induced the early apoptosis in a force and frequency and time-dependent *** the presence of LPS,mechanical stretch enhanced LPS-induced early apoptosis,especially in 100 ng/mL IPS group compared with 1 ng/ mL LPS and the control *** stretch increased il-8 production and enhanced LPS-induced il-8 screation both in mRNA and protein ***:Mechanical stretch can induce the early apoptosis and il-8 *** stretch and LPS have an addictive effect on the early apoptosis and il-8 production in alveolar type 2 cells,which is one of the mechanisms of ventilator-induced lung injury.

关键词： Mechanical stretch Early apoptosis Human alveolar typeⅡepithelial cells Lipopolysaccharide il-8

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TRAil-induced expression of uPA and il-8 strongly enhanced by overexpression of TRAF2 and Bcl-xL in pancreatic ductal adenocarcinoma cells

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Hepatobiliary & Pancreatic Diseases International 2013年第1期12卷 94-98页

作者： Dong-Hui Zhou Li-Na Yang Christian Rder Holger Kalthoff Anna Trauzold Department of Oncology First Affiliated HospitalZhejiang University School of Medicine Division of Molecular Oncology Institute of Experimental Cancer ResearchCCC-NorthUniversity Hospital Schleswig-HolsteinCampus Kiel24105 KielGermany

BACKGROUND:The death ligand,tumor necrosis factor(TNF)related apoptosis-inducing ligand(TRAil),induces apoptosis and non-apoptotic signaling in some tumor *** purpose of this study was to investigate the roles of the pro-apoptotic TRAil receptors,TRAil-R1 and TRAil-R2,as well as Bcl-xL and TRAF2 in TRAil-induced expression of the pro-inflammatory cytokine il-8 and the invasion-promoting protein urokinase(uPA) in pancreatic ductal adenocarcinoma(PDAC) ***:Colo357wt,Colo357/TRAF2,Colo357/Bcl-xL,Panc89 and PancTuI cells were stimulated with TRAil and uPA and il-8 expression was detected using real-time ***,receptor-specific antibodies were used to investigate the effects of TRAil-R1 or TRAil-R2 ***:Dose-dependent increases in uPA and il-8 expression were detected following TRAil stimulation in PDAC *** effects were inhibited when TRAil-R1 but not TRAil-R2 was *** of TRAF2 or Bcl-xL strongly increased TRAil-mediated upregulation of uPA and ***:In PDAC cells,TRAil strongly induced uPA and il-8 via *** response was further enhanced in cells overexpressing TRAF2 and ***,inhibition of the non-apoptotic "side-effects" of TRAil treatments by inactivation of TRAF2 and Bcl-xL might represent additional relevant strategies for the treatment of pancreatic cancer.

关键词： TRAil uPA il-8 Bcl-xL pancreatic cancer cell

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Effect of Yinxieling decoction on PASI,TNF-α and il-8 in patients with psoriasis vulgaris

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Asian Pacific Journal of Tropical Medicine 2014年第8期7卷 668-670页

作者： Yong-Jiang Dai Yu-Yang Li Hui-Ming Zeng Xiong-An Liang Zhi-Jie Xie Zhi-Ang Zheng Qin-Hui Pan Yi-Xiong Xing Department of Dermatology Affiliated Hospital of Hainan Medical College Department of Dermatology Sanya Agricultural Reclamation Hospital

Objective:To study the effect of Yinxieling decoction on PASI,TNF-α and il-8 in patients with psoriasis ***:A total of 120 cases of psoriasis vulgaris were divided into 4 groups according to syndrome differentiation of TCM and randomized controlled method:wind heat syndrome group(group A).blood stasis syndrome group(group B) blood dryness syndrome group(group C)nd control group(group D)(n=30 per group).Patients in observation groups were treated with Yinxieling decoction,while patients in control group were treated by placebo for 8 *** of TNT-α and il-8 were determined before treatment.4 and 8 weeks after *** area and severity index score was also performed before and after ***:psoriasis area and severity index score and serum level of TNF-α,il-8 were significantly decreased in all *** decrease in three observation groups was more significant(P8,respectively(Pil-8.

关键词： Psoriasis vulgaris Yinxieling decoction Syndrome differentiation TNF-α il-8

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Effect of curcumin on expressions of NF-κBp65,TNF-αand il-8 in placental tissue of premature birth of infected mice

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Asian Pacific Journal of Tropical Medicine 2017年第2期10卷 168-171页

作者： Yan-Zi Guo Ping He Ai-Min Feng The Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine XianyangShaanxi ProvinceChina

Objective:To observe the effect of curcumin on expressions of nuclear transcription factorkappa Bp65(NF-κBp65),TNF--α and il-8 in placental tissue of premature birth of infected mice induced by lipopolysaccharide(LPS).Methods:A total of 60 C57BL/6 mice pregnant with 15 d were collected and randomly divided into control group,model group,treatment group and preventative *** was repeatedly injected in abdominal cavity to construct infected premature birth model,while mice of control group were given with 100 mg/kg of vitamin C through abdominal cavity injection and mice of treatment group and preventative group were given curcumin of 100 mg/kg through abdominal cavity injection after modeling operation and before 1 d of modeling operation,respectively.A total of 5 mice of four groups respectively were executed by cervical dislocation after 6 h,12 h and 24 h after constructing *** tissues were collected and the immunohistochemical mothod SABC of immunologic tissue was used to detect the expression of NF-d mice after 24 h was collected tκBp65,TNF-o detect the co-and il-8 and peripheral blood of executencentrations of il-8,malondialdehyde(MDA) and superoxide dismutase(SOD),meanwhile live birth rate of four groups was ***:Staining intensity of NF-tissue of treatment group and preventative group was κBp65,TNF-significantly-αand il-8 in placental higher than control group but lower than model group(Pil-8 and MDA of control group was significantly lower than the other three groups(Pil-8 and MDA of treatment group and preventative group were significantly lower than model group(Pile level of SOD was significantly higher than model group(P<0.05).Live birth rate of treatment group and preventative group was significantly higher than model group(P<0.05).Conclusions:Curcumin can effectively prevent the a

关键词： Curcumin Premature birth induced with infection LPS NF-κ Bp65 TNF-α il-8

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EXPRESSION OF il-6, sgp130, il-8 AND THEIR RECEPTORS INACUTE PROMYELOCYTIC LEUKEMIA DURING ALL-TRANSRETINOIC ACID INDUCTION TREATMENT

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Chinese Journal of Cancer Research 1999年第4期11卷 271-274页

作者：曾慧兰张学光陈子兴陶瑞芳邱月华张毅孙爱宁王爱青王玮林宝爵 Department of Hematology The First Affiliated Hospital Jinan University Medical College Guangzhou China Suzhou Medical College Suzhou Jiangsu Province China

Objective: To evaluate the expression and its clinical significance of interleukin 6 (il-6), soluble glycoprotein 130 (sgp130), interleukin 8 (il-8) and type A interleukin 8 receptor (il-8RA) in acute promyelocytic leukemia (APL) patients during all-trans retinoic acid (ATRA) induction treatment. Methods: Plasma and bone marrow mononuclear cell (MNC) culture supernatant il-6, sgp130, il-8 concentration of 18 cases with APL were kinetically measured in vivo and in vitro (ELISA). Bone marrow MNC il-8RA was measured by flow cytometry after being cultured with ATRA (10?6mmol/L). Results: Plasma il-6, sgp130, il-8 levels were higher than normal (Pil-6, spg130 levels correlated with white blood cell (WBC) counts (Pile il-8 levels correlated with body temperature (Pil-6 of bone marrow MNC culture supernatant did not change, that of sgp130 mildly decreased, and il-8 significantly decreased while the positive rate of il-8RA on bone marrow MNC increased. During ATRA treatment, plasma il-6 changes were correlated with WBC counts. Peak levels of il-6 and WBC were lower in patients who received intermittent therapy than those who received continuous therapy. Plasma il-6 and il-8 were increased when complicated with infection and il-8 seemed more sensitive. Conclusion: Plasma il-6, sgp130, il-8 levels may reflect patients' responsiveness to ATRA treatment, and could be used to predict hyperleukocytosis and intercurrent infection. ATRA induces APL cell differentiation possibly via sgp130 signal transducer chain. Measurement of sgp130 had certain meaning to prognosis.

关键词： Leukemia Premyelocytic Retinoic acid il-6 Glycoprotein-130 il-8 Receptor

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il-8通过激活PKC/ERK信号通路促进肾癌细胞上皮细胞-间质细胞转化

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生物化学与生物物理进展 2012年第10期39卷 981-986页

作者：毕良宽林天歆许可慰韩金利黄海张彩霞董文刘皓黄健中山大学孙逸仙纪念医院泌尿外科广州510120

上皮细胞-间质细胞转化(EMT)在肿瘤转移方面起着非常重要的作用.肾癌发生EMT的具体分子机制尚不清楚.il-8是一个重要的炎症趋化因子,研究表明肾癌细胞可以分泌il-8,但il-8是否参与肾癌细胞EMT的调节目前尚无报道.我们研究发现,il-8可以... 详细信息

上皮细胞-间质细胞转化(EMT)在肿瘤转移方面起着非常重要的作用.肾癌发生EMT的具体分子机制尚不清楚.il-8是一个重要的炎症趋化因子,研究表明肾癌细胞可以分泌il-8,但il-8是否参与肾癌细胞EMT的调节目前尚无报道.我们研究发现,il-8可以促进肾癌细胞形态发生间质化改变,il-8刺激后E-钙黏蛋白表达水平下降,N-钙黏蛋白表达上调.另外,il-8可以促进肾癌细胞侵袭,但对肾癌细胞增殖的影响并不明显.进一步研究显示,il-8通过激活蛋白激酶C(PKC)引起细胞外调节性激酶(ERK)磷酸化.因此,我们认为il-8可能通过PKC/ERK信号通路促进肾癌细胞发生EMT,这可能是肾癌转移的重要机制之一.

关键词：肾癌 il-8 上皮细胞-间质细胞转化蛋白激酶C 细胞外信号调节性激酶(ERK)

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il-8与透析膜的生物相容性

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复旦学报（医学版） 2002年第3期29卷 232-234页

作者：钟一红徐元钊丁小强复旦大学附属中山医院肾脏内科上海200032

血液透析（HD）是治疗终末期肾脏病的主要方法之一。随着血液净化技术的发展和透析器膜材料的改进，提高透析质量，减少透析过程中不良反应的发生，日益受到人们的关注。HD是一种非生理过程，血液中的单核细胞（PBMC）可以由血膜的直接... 详细信息

血液透析（HD）是治疗终末期肾脏病的主要方法之一。随着血液净化技术的发展和透析器膜材料的改进，提高透析质量，减少透析过程中不良反应的发生，日益受到人们的关注。HD是一种非生理过程，血液中的单核细胞（PBMC）可以由血膜的直接接触、补体激活以及细菌内毒素及其片段而被激活，产生多种细胞因子。这些细胞因子中白介素（il-1、2、6）以及肿瘤坏死因子（TNF-α），已被证实与透析过程中的发热、头痛、恶心、肌肉酸痛、低血压以及长期透析出现的营养不良相关。近来又有多篇文献报道白细胞介素8（il-8）也与透析膜的生物相容性密切相关。生物相容性差的透析膜可引起血浆il-8的明显升高。il-8参与了透析过程中-过性白细胞减少、肺毛细血管内的白细胞滞留、低氧血症、低血压和透析相关性关节炎的急性发作，并造成长期血透患者的抗感染能力下降。现就透析膜的生物相容性与il-8的关系，试图从分子生物学角度进一步探讨HD相关并发症的机制，为临床采取相应治疗提供理论基础。

关键词： il-8 透析膜生物相容性血液透析终末期肾病透析相关并发症

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