The interaction between tumor necrosis factor-like weak inducer of apoptosis and its receptor fibroblast growth factor-inducible 14 promotes the recruitment of neutrophils into the ischemic brain

• Type of Material: Article
• Authors: Woldeab B Haile, Emory University; Ramiro Echeverry, Emory University; Jialing Wu, Emory University; Manuel Yepes, Emory University
• Language: English
• Date: 2010-06
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Nature Publishing Group
• Final Published Version (URL): http://www.nature.com/jcbfm/journal/v30/n6/full/jcbfm2009280a.html
• Title of Journal or Parent Work: Journal of Cerebral Blood Flow and Metabolism
• ISSN: 0271-678X
• Volume: 30
• Issue: 6
• Start Page: 1147
• End Page: 1156
• Grant/Funding Information: This work was supported in part by National Institutes of Health Grants NS-062073 and HL-095063 (to MY).
• Keywords: neutrophils; fibroblast growth factor-inducible 14 (Fn14); cerebral ischemia; tumor necrosis factor-like weak inducer of apoptosis (TWEAK); monocyte chemoattractant protein-1 (MCP-1)
• Research Categories: Health Sciences, General; Biology, Neuroscience; Biology, Physiology

Abstract

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are expressed in endothelial cells and perivascular astrocytes. Here, we show that TWEAK induces a dose-dependent increase in the expression of the chemokine monocyte chemoattractant protein-1 (MCP-1) in astrocytes, and that this effect is mediated by its interaction with Fn14 via nuclear factor-κB pathway activation. Exposure to oxygen-glucose deprivation (OGD) conditions increases TWEAK and Fn14 mRNA expression in wild-type (Wt) astrocytic cultures. Likewise, incubation under OGD conditions induces the expression of MCP-1 in Wt astrocytes but not in astrocytes deficient on either TWEAK (TWEAK−/−) or Fn14 (Fn14−/−). We also found that TWEAK induces the passage of neutrophils to the abluminal side of an in vitro model of the blood–brain barrier. Our earlier studies indicate that cerebral ischemia increases the expression of TWEAK and Fn14 in the endothelial cell-basement membrane-astrocyte interface. Here, we report that middle cerebral artery occlusion increases the expression of MCP-1 and the recruitment of neutrophils into the ischemic tissue in Wt but not in TWEAK−/− or Fn14−/− mice. These novel results indicate that during cerebral ischemia, the interaction between TWEAK and Fn14 leads to the recruitment of leukocytes into the ischemic tissue.