TRAIL facilitates cytokine expression and macrophage migration during hypoxia/reoxygenation via ER stress-dependent NF-κB pathway. (February 2017)

• Record Type: Journal Article
• Authors: Jiang, Yinan; Chen, Xiaoyan; Fan, Mengya; Li, Hui; Zhu, Weina; Chen, Xi; Cao, Chenghua; Xu, Rui; Wang, Yaohui; Ma, Yuanfang
• Is Part Of: Molecular immunology. Volume 82(2017:Feb.)
• Page Start: 123
• Page End: 136
• Publication Date: 2017-02
• Subjects: TRAIL Tumor necrosis factor-related apoptosis-inducing ligand -- I/R Ischemia and reperfusion -- H/R Hypoxia and reoxygenation -- CAPE Cafifeic Acid Phenethyl Ester -- ER stress Endoplasmic reticulum stress -- Neutr Ab Neutralizing antibody -- ARVMs adult rat ventricular myocytes; TRAIL -- Macrophages -- Cytokine expression -- NF-κB -- ER stress; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2016.12.023
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: TRAIL facilitated macrophage inflammatory factors production macrophage migration after hypoxia and reperfusion. Production of macrophage cytokines induced by TRAIL dependent on activation of NF-κB and ER stress pathway. ER stress signaling pathway contributed to the activation of the NF-κB signaling 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.