Down-regulation of inducible nitric oxide synthase and tumor necrosis factor-alpha expression by bisphenol A via nuclear factor-kappaB inactivation in macrophages.
Bisphenol A [BPA, 2,2bis(4hydroxyphenyl)propane] is reported to have estrogenic activity; however, its influence on cytokine production or immune system function remains unclear. In this study, we investigated the effects of BPA on the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), and on the level of inducible nitric oxide synthase (iNOS) and TNF-alpha gene expression in mouse macrophages. BPA alone did not affect NO or TNF-alpha production. In contrast, BPA inhibited lipopolysaccharide (LPS)-induced NO and TNF-alpha production, and the levels of iNOS and TNF-alpha mRNA in a dose-dependent manner. Treatment with ICI 182.780, an estrogenreceptor antagonist, inhibited the suppressive effects of BPA. Transient expression and electrophoretic mobility shift assays with NF-kappaB binding sites revealed that BPA reduced the levels of the LPS-induced NF-kappaB transcription factor complex. These results demonstrate that BPA may affect the regulation of the immune system function by reducing NO and TNF-alpha production via the inhibition of NF-kappaB transactivation mediated through the estradiol receptor.
Kim
Ji Young
JY
Department of Pharmacy, College of Pharmacy, Chosun University, 375 Seosuk-dong, Kwangju 501-759, South Korea.
Jeong
Hye Gwang
HG
D000818:Animals; D001559:Benzhydryl Compounds; D002478:Cells, Cultured; D015536:Down-Regulation; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010636:Phenols / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004958:Estradiol; D004965:Estrogen Antagonists; D000077267:Fulvestrant; D016328:NF-kappa B; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010636:Phenols; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; C496317:Nos2 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds