Role of NADPH oxidase 4 in lipopolysaccharide-induced proinflammatory responses by human aortic endothelial cells

Hye Sun Park, Jung Nyeo Chun, Hye Young Jung, Chulhee Choi, Yun Soo Bae

Research output: Contribution to journalArticlepeer-review

176 Scopus citations

Abstract

Objective: We investigated the role of NADPH oxidase 4 (Nox4) on lipopolysaccharide (LPS)-induced proinflammatory responses by human aortic endothelial cells (HAECs). Methods and results: Yeast two-hybrid and glutathione-S-transferase pull-down assays indicated that the cytosolic Toll/IL-1R region of Toll-like receptor 4 (TLR4) (amino acids 739-769) is the responsible domain for interaction with the COOH terminal of Nox4 (amino acids 451-530). Consistently, overexpression of the COOH-terminal region of Nox4 inhibited nuclear factor-κB activation in response to LPS. Downregulation of Nox4 by transfection of siRNA specific to Nox4 in HAECs resulted in a failure to induce reactive oxygen species (ROS) generation and subsequent expression of intercellular adhesion molecule-1 (ICAM-1) and chemokines such as IL-8 and monocyte chemoattractant protein-1 (MCP-1) in response to LPS. Furthermore, transient transfection of endothelial cells with Nox4 siRNA led to a decrease in migration and adhesion of monocytes in response to LPS by 36% and 52%, respectively. Conclusions: Nox4 plays a central role in LPS-induced proinflammatory responses by endothelial cells in an ROS-dependent manner.

Original languageEnglish
Pages (from-to)447-455
Number of pages9
JournalCardiovascular Research
Volume72
Issue number3
DOIs
StatePublished - 1 Dec 2006

Keywords

  • Atherosclerosis
  • Endothelial cells
  • Lipopolysaccharide
  • NADPH oxidase 4
  • Reactive oxygen species
  • Toll-like receptor 4

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