Parabens, including the most common methylparaben (MeP), are popular preservatives, which possess estrogenic activity. The aims of this study were to assess the impact of MeP on estrogen receptors (ERs) and/or NF-κB-dependent generation of IL-8 and production of nitric oxide (NO), and also to verify the hypothesis about the crosstalk of ERs with NF-κB in xenoestrogen-exposed neutrophils. Human neutrophils were incubated for 20-h with MeP (0.06 μM) and/or ER antagonist (1 μM) and/or NF-κB inhibitor (100 μM). After the isolation of cell lysates and cytoplasmic and nuclear fraction, the expression of ERα, ERβ, p-IKKα/β, p65 NF-κB, and inducible nitric oxide synthase (iNOS) was measured by Western blot analysis, The concentration of NO was evaluated by Griess reaction, and that of IL-8 was measured by ELISA. The results showed that MeP modulated the expression of ERα, but not ERβ. Exposure to paraben activated iKKα/β-dependent NF-κB pathway, but translocation of p65 NF-κB into the cell nucleus was inhibited by ERs. MeP also decreased the iNOS-dependent production of NO, but did not influence the secretion of IL-8 by neutrophils. The study indicates that MeP may affect the functioning of human neutrophils by modulating intracellular signal transduction pathways, including ERs and NF-κB pathway.
Keywords: Endocrine disrupting chemicals; Estrogen receptors; NF-κB; Parabens; Xenoestrogens.
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