title: TRAIL facilitates cytokine expression and macrophage migration during hypoxia/reoxygenation via ER stress-dependent NF-κB pathway.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is known as a key molecule to induce cancer cell apoptosis, has also been found to participate in the process of ischemia/reperfusion (I/R) injury. Infiltrated macrophages play dual roles in inflammatory injury and healing following I/R. Whether TRAIL has any effect on macrophages during this process remains elusive. Here we showed that I/R triggered the expressions of TRAIL, DR5 and cytokines (IL-1β, TNFα, CCL-2 and ICAM-1), in addition to macrophage infiltration, which could be abolished by TRAIL neutralizing antibody. In vitro, TRAIL enhanced DR5 expression and facilitated the macrophages migration following hypoxia/reoxygenation (H/R) treatment in a dose-dependent manner via ER stress and NF-κB signaling pathways, which is accompanied by inflammatory factors expression. The increased cytokines production (such as TNFα and IL-1β) stimulated by TRAIL can be blocked by the NF-κB and ER stress inhibitor. The results also suggested that NF-κB activation of macrophages during H/R was regulated by ER stress. Thus, our research present that TRAIL affects functional activities of macrophages during I/R injury, which may be a potential therapeutic target for ischemic heart disease.
authors.affiliation: School of Basic Medical Science, Zhengzhou University, Zhengzhou, Henan 450002, China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Medical College of Henan University, Kaifeng, Henan 475004, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Medical College of Henan University, Kaifeng, Henan 475004, China.
authors.forename: Mengya
authors.initials: M
authors.lastname: Fan
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Medical College of Henan University, Kaifeng, Henan 475004, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Medical College of Henan University, Kaifeng, Henan 475004, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Medical College of Henan University, Kaifeng, Henan 475004, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Medical College of Henan University, Kaifeng, Henan 475004, China.
authors.forename: Chenghua
authors.initials: C
authors.lastname: Cao
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Medical College of Henan University, Kaifeng, Henan 475004, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Medical College of Henan University, Kaifeng, Henan 475004, China. Electronic address: wangyaohui2001@sina.com.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Basic Medical Science, Zhengzhou University, Zhengzhou, Henan 450002, China; Henan Key Laboratory of Engineering Antibody Medicine, Medical College of Henan University, Kaifeng, Henan 475004, China. Electronic address: mayf@henu.edu.cn.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D059865:Endoplasmic Reticulum Stress / Q000276:immunology; D005434:Flow Cytometry; D015151:Immunoblotting; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D053221:TNF-Related Apoptosis-Inducing Ligand; C505655:Tnfsf10 protein, rat
keywords: Cytokine expression; ER stress; Macrophages; NF-κB; TRAIL