17beta-estradiol inhibits NADPH oxidase activity through the regulation of p47phox mRNA and protein expression in THP-1 cells.
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.
Sumi
Daigo
D
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65, Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Hayashi
Toshio
T
Matsui-Hirai
Hisako
H
Jacobs
Aaron T
AT
Ignarro
Louis J
LJ
Iguchi
Akihisa
A
D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016328:NF-kappa B; D010750:Phosphoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D007371:Interferon-gamma; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1