title: Interleukin 17A exacerbates atherosclerosis by promoting fatty acid-binding protein 4-mediated ER stress in macrophages.
abstract: BACKGROUND
  Apoptosis and fatty acid-binding protein-4 (FABP4) induced-endoplasmic reticulum (ER) stress in macrophage is an important pathological process in several vascular occlusive diseases, including atherosclerosis, both of which are accelerated by lipids or inflammatory cytokines.
  
  
  OBJECTIVE
  To determine whether interleukin 17A (IL-17A) accelerates atherosclerosis through activating FABP4-mediated ER stress in macrophage.
  
  
  RESULTS
  We show here that IL-17A induced ER stress in both murine and human-derived macrophages in vitro, and in the atherosclerotic lesions of ApoE-/- mice. Treating ApoE-/- mice with a chemical chaperone alleviated IL-17A-mediated ER stress and macrophage apoptosis, which was accompanied by recovered atherogenesis. Mechanistically, IL-17A up-regulated the expression of FABP4 (aP2), a cytosolic lipid chaperone that is able to promote lipid-induced macrophage ER stress, through NF-κB and ERK/p38 mitogen-activated protein kinase (MAPK) pathways in macrophages. The inhibition of aP2 expression with a specific chemical inhibitor significantly blocked IL-17A-accelerated ER stress and apoptosis in plaque, and partially rescued IL17A-induced atherogenesis.
  
  
  CONCLUSIONS
  The data collectively establish a previously unrecognized link between IL-17A and ER stress through cytosolic lipid chaperone aP2 in macrophages and provide a new insight for understanding the role of IL-17A in atherosclerosis.
authors.affiliation: Department of Immunology, Shandong University School Medicine, Shandong, P.R. China.
authors.forename: Qi
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authors.lastname: Gao
authors.forename: Yang
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authors.lastname: Jiang
authors.forename: Shen
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authors.lastname: Dai
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.forename: Faliang
authors.initials: F
authors.lastname: Zhu
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Jining
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authors.lastname: Wang
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Shi
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wanjun
authors.initials: W
authors.lastname: Chen
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang