Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells

Norihiro Harada, Masafumi Nakayama, Hiroyasu Nakano, Yoshinosuke Fukuchi, Hideo Yagita, Ko Okumura

Research output: Contribution to journalArticlepeer-review

156 Citations (Scopus)

Abstract

TWEAK, a member of the TNF family, induces cell death in some tumor cell lines, but also induces proliferation of endothelial cells and angiogenesis. Recently, fibroblast growth factor-inducible 14 (Fn14) has been identified to be a TWEAK receptor, which may be responsible for the proliferation of endothelial cells and angiogenesis. In this study, we investigated the pro-inflammatory effect of TWEAK on human umbilical vein endothelial cells (HUVEC). We demonstrated that TWEAK could not only induce the proliferation and migration but also upregulate the cell surface expression of adhesion molecules such as ICAM-1 and E-selectin, and induce the secretion of chemokines such as IL-8 and MCP-1 in HUVEC. Moreover, by using an anti-Fn14 mAb that blocks the TWEAK/Fn14 interaction, we demonstrated that Fn14 was constitutively expressed on HUVEC and totally mediated the biological effects of TWEAK on HUVEC. These results indicated that TWEAK could induce pro-inflammatory reactions via Fn14 on HUVEC.

Original languageEnglish
Pages (from-to)488-493
Number of pages6
JournalBiochemical and biophysical research communications
Volume299
Issue number3
DOIs
Publication statusPublished - 2002

Keywords

  • Adhesion molecules
  • Chemokines
  • Endothelial cells
  • NF-κB
  • TNF

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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