Down-regulation of inducible nitric oxide synthase and tumor necrosis factor-α expression by bisphenol A via nuclear factor-κB 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-α (TNF-α), and on the level of inducible nitric oxide synthase (iNOS) and TNF-α gene expression in mouse macrophages. BPA alone did not affect NO or TNF-α production. In contrast, BPA inhibited lipopolysaccharide (LPS)-induced NO and TNF-α production, and the levels of iNOS and TNF-α 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-κB binding sites revealed that BPA reduced the levels of the LPS-induced NF-κB transcription factor complex. These results demonstrate that BPA may affect the regulation of the immune system function by reducing NO and TNF-α production via the inhibition of NF-κB transactivation mediated through the estradiol receptor.