Inhibition of vascular inflammation by dehydroepiandrosterone sulfate in human aortic endothelial cells: Roles of PPARα and NF-κB

Robin Altman, Deborah Motton, Rama S. Kota, John C. Rutledge

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Dehydroepiandrosterone sulfate (DHEAS) is a hormone produced by the adrenal gland and is a precursor for both androgens and estrogens. Atherosclerosis is a well characterized inflammatory disease, but little is known about the role of DHEAS in vascular inflammation. We hypothesize that DHEAS can reduce inflammation in vascular endothelial cells and the mechanism involves the peroxisome proliferator-activated receptor α (PPARα), thereby inhibiting transcription factors involved in endothelial cell inflammation. To test our hypothesis, aortic endothelial cells were pretreated for 48 h with DHEAS, then with TNF-α. TNF-α-induced upregulation of the expression of inflammatory genes interleukin (IL)-8 and intracellular adhesion molecule (ICAM)-1 was attenuated by incubation with DHEAS. DHEAS inhibited the TNF-α-induced surface expression of vascular cell adhesion molecule (VCAM)-1. This effect was abolished by the addition of MK866, a PPARα inhibitor, indicating that PPARα is involved in the mechanism of this inhibition. The addition of the aromatase inhibitor letrozole had no effect on the inhibition of TNF-α-induced VCAM-1 expression by DHEAS. Treatment of endothelial cells with DHEAS dramatically inhibited the TNF-α-induced activation of NF-κB, an inflammatory transcription factor, and increased protein levels of the NF-κB inhibitor, IκB-α. These results signify the ability of DHEAS to directly inhibit the inflammatory process and show a potential direct effect of DHEAS on vascular inflammation that has implications for the development of atherosclerotic cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)76-84
Number of pages9
JournalVascular Pharmacology
Volume48
Issue number2-3
DOIs
StatePublished - Feb 2008

Keywords

  • Dehydroepiandrosterone sulfate
  • Endothelial cell
  • Inflammation
  • PPAR
  • VCAM

ASJC Scopus subject areas

  • Pharmacology

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