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AP-1 and NF-κB transcriptionally regulate interleukin-8 in EA.Hy926 cells under shear stress

Yi Zhang1, Yi Lai, Huai-Qing Chen

  • 1Laboratory of Biomedical Ultrasonics and Gynecologic Cancers, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China.

Cell Biology International
|September 8, 2011
PubMed

Insights

Shear stress (SS) significantly increases interleukin-8 (IL-8) mRNA expression in endothelial cells. This process involves activator protein 1 (AP-1) and nuclear factor-kappa B (NF-κB) activation, driving inflammation.

Area of Science:

  • Cardiovascular biology
  • Molecular biology
  • Inflammation research

Background:

  • Cardiovascular and cerebrovascular diseases are leading global causes of death.
  • Atherosclerosis (AS) is an inflammatory disorder influenced by chemokines and blood shear stress (SS).
  • Interleukin-8 (IL-8) is a key chemokine implicated in inflammatory processes.

Purpose of the Study:

  • To investigate the effect of SS on IL-8 mRNA expression in human endothelial cells (EA.Hy926).
  • To elucidate the transcriptional mechanisms, specifically the roles of AP-1 and NF-κB, in SS-induced IL-8 production.

Main Methods:

  • Human endothelial cells (EA.Hy926) were exposed to varying intensities and durations of SS.
  • IL-8 mRNA expression levels were quantified.
  • Reporter gene assays using wild-type and mutated IL-8 promoter constructs (targeting AP-1 and NF-κB binding sites) were performed.
  • NF-κB pathway activation (p65 translocation, IκB degradation) was monitored.

Main Results:

  • IL-8 mRNA expression increased with SS intensity and duration.
  • Both AP-1 and NF-κB binding sites in the IL-8 promoter were essential for SS-induced transcription.
  • NF-κB activation occurred rapidly (within minutes), with p65 translocation and IκB degradation observed under low SS.
  • Combined activation of NF-κB and AP-1 were identified as upstream regulators.

Conclusions:

  • Low shear stress activates the NF-κB and AP-1 pathways in EA.Hy926 cells.
  • This activation leads to increased IL-8 production, initiating an inflammatory response in the endothelium.
  • Findings highlight the role of shear stress in regulating endothelial inflammation relevant to atherosclerosis.

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