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

AbstractIn this report, we demonstrate that NADPH oxidase is activated by tumor necrosis factor-α (TNF-α) plus interferon-γ (IFN-γ) in human monocytic cells (THP-1 cells) differentiated with phorbol ester (PMA) and that physiological concentration of 17β-estradiol inhibits NADPH oxidase activity in THP-1 cells stimulated with TNF-α plus IFN-γ. This effect is mediated by estrogen receptor based on estrogen receptor antagonist (ICI 182, 780) that diminishes inhibition by 17β-estradiol. This inhibition is specific in 17β-estradiol because 17α-estradiol, testosterone and progesterone do not inhibit NADPH oxidase activity. Activation of NADPH oxidase induced by TNF-α plus IFN-γ is caused by up-regulation of p47phox (cytosolic component of NADPH oxidase) expression. 17β-Estradiol prevents the up-regulation of p47phox mRNA and protein expression. This prevention of p47phox expression depends on the inhibition of NF-κB activation. Our results implicate that 17β-estradiol has an anti-atherosclerotic effects through the improvement of nitric oxide (NO) bioavailability caused by the regulation of superoxide (O2−) production