17beta-estradiol inhibits NADPH oxidase activity through the regulation of p47phox mRNA and protein expression in THP-1 cells

Biochim Biophys Acta. 2003 May 12;1640(2-3):113-8. doi: 10.1016/s0167-4889(03)00026-0.

Abstract

In this report, we demonstrate that NADPH oxidase is activated by tumor necrosis factor-alpha (TNF-alpha) plus interferon-gamma (IFN-gamma) in human monocytic cells (THP-1 cells) differentiated with phorbol ester (PMA) and that physiological concentration of 17beta-estradiol inhibits NADPH oxidase activity in THP-1 cells stimulated with TNF-alpha plus IFN-gamma. This effect is mediated by estrogen receptor based on estrogen receptor antagonist (ICI 182, 780) that diminishes inhibition by 17beta-estradiol. This inhibition is specific in 17beta-estradiol because 17alpha-estradiol, testosterone and progesterone do not inhibit NADPH oxidase activity. Activation of NADPH oxidase induced by TNF-alpha plus IFN-gamma is caused by up-regulation of p47(phox) (cytosolic component of NADPH oxidase) expression. 17beta-Estradiol prevents the up-regulation of p47(phox) mRNA and protein expression. This prevention of p47(phox) expression depends on the inhibition of NF-kappaB activation. Our results implicate that 17beta-estradiol has an anti-atherosclerotic effects through the improvement of nitric oxide (NO) bioavailability caused by the regulation of superoxide (O(2)(-)) production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Estradiol / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interferon-gamma / pharmacology
  • NADPH Oxidases / antagonists & inhibitors*
  • NF-kappa B / antagonists & inhibitors
  • Phosphoproteins / genetics*
  • RNA, Messenger / analysis
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • NF-kappa B
  • Phosphoproteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Estradiol
  • Interferon-gamma
  • NADPH Oxidases
  • neutrophil cytosolic factor 1