IL-8 Triggers Neutrophil Extracellular Trap Formation Through an Nicotinamide Adenine Dinucleotide Phosphate Oxidase- and Mitogen-Activated Protein Kinase Pathway-Dependent Mechanism in Uveitis

作者全名："Shu, Qinxin; Zhang, Ni; Liu, Yanyao; Wang, Xing; Chen, Jinquan; Xie, Hao; Pan, Fuying; Zhao, Long; Ding, Xuanheng; Wen, Yan; Wang, Lingda; Xie, Wenxi; Lu, Jing; Su, Guannan; Peng, Hui; Yang, Peizeng"

作者地址："[Shu, Qinxin; Zhang, Ni; Wang, Xing; Chen, Jinquan; Xie, Hao; Pan, Fuying; Zhao, Long; Ding, Xuanheng; Wen, Yan; Wang, Lingda; Xie, Wenxi; Lu, Jing; Su, Guannan; Peng, Hui; Yang, Peizeng] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst,Chongqing Key Lab Ophthalmol, Chongqing Branch Municipal Div,Natl Clin Res Ctr, Chongqing, Peoples R China; [Liu, Yanyao] Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Chongqing, Peoples R China"

通信作者："Peng, H; Yang, PZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001169492500009

JCR分区：Q1

影响因子：5

年份：2023

卷号：64

期号：13

开始页：　

结束页：　

文献类型：Article

关键词：Behcet; uveitis; interleukin-8; neutrophil extracellular traps

摘要："PURPOSE. To explore the mechanism underlying IL-8-induced neutrophil extracellular trap (NET) formation in patients with ocular-active Behcet's disease (BD) and the effect of inhibiting NET formation on the severity of inflammation in experimental autoimmune uveitis (EAU) mice. METHODS. The serum extracellular DNA and neutrophil elastase (NE) and IL-8 levels in patients with ocular-active BD, the expression of myeloperoxidase, NE, and histone H3Cit in IL-8-induced neutrophils isolated from healthy controls, and the effects of NETs on HMC3 cells were detected. Female C57BL/6J mice were immunized with IRBP651- 670 to induce EAU and EAU mice received intravitreal injection of the CXCR2 (IL-8 receptor) antagonist SB225002 or PBS. The serum levels of extracellular DNA, NE, and keratinocyte-derived chemokine (the mouse ortholog of human IL-8) and expression of myeloperoxidase, NE, and histone H3Cit in mouse retinas were detected. Disease severity was evaluated by clinical and histopathological scores. RESULTS. Serum keratinocyte-derived chemokine expression levels in EAU mice and IL-8 expression levels in patients with ocular-active BD increased. IL-8 notably increased NET formation in a dose-dependent manner through an nicotinamide adenine dinucleotide phosphate oxidase and mitogen-activated protein kinase pathway dependent mechanism. IL-8-induced NET formation damaged HMC3 cells in vitro. Pretreatment with SB225002 notably ameliorated the production of NETs in EAU mice. CONCLUSIONS. Our data confirm that NET formation is induced by IL-8. IL-8-induced NET formation was found to be related to mitogen-activated protein kinase and nicotinamide adenine dinucleotide phosphate pathways. Pretreatment with the CXCR2 antagonist SB225002 alleviated neutrophil infiltration and suppressed NET formation in EAU mice."

基金机构：National Natural Science Foundation of China [81900845]; National Natural Science Foundation Key Program (China) [82230032]; Chongqing Key Laboratory of Ophthalmology (Chongqing Science Technology Committee) [2008CA5003]; Chongqing Science & Technology Platform and Base Construction Program [cstc2014pt-sy10002]

基金资助正文："Supported by funds from the National Natural Science Foundation of China (No. 81900845), the National Natural Science Foundation Key Program (China) (No. 82230032), the Chongqing Key Laboratory of Ophthalmology (Chongqing Science Technology Committee, No. 2008CA5003), and the Chongqing Science & Technology Platform and Base Construction Program (No. cstc2014pt-sy10002)."