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Methylparaben-induced regulation of estrogenic signaling in human neutrophils
Karolina Nowak1, Ewa Jabłońska1, Marzena Garley1
1Department of Immunology, Medical University of Bialystok, Poland.
Abstract:
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.
Insights
Methylparaben (MeP), a common preservative, impacts human neutrophils by affecting estrogen receptors (ERs) and the NF-κB pathway. MeP modulates ERα, influences NF-κB signaling, and decreases nitric oxide production.
Area of Science:
- Endocrinology
- Immunology
- Toxicology
Background:
- Parabens, widely used preservatives, exhibit estrogenic activity.
- Methylparaben (MeP) is a prevalent paraben with known estrogenic effects.
- Neutrophils play a crucial role in immune responses and can be influenced by environmental chemicals.
Purpose of the Study:
- To investigate the effects of MeP on estrogen receptors (ERs) and NF-κB signaling in human neutrophils.
- To assess MeP's impact on interleukin-8 (IL-8) and nitric oxide (NO) production.
- To explore potential crosstalk between ERs and NF-κB pathways in neutrophils exposed to xenoestrogens.
Main Methods:
- Human neutrophils were treated with MeP, an ER antagonist, and/or an NF-κB inhibitor.
- Western blot analysis was used to measure the expression of ERα, ERβ, p-IKKα/β, p65 NF-κB, and iNOS.
- Nitric oxide levels were quantified using the Griess reaction, and IL-8 secretion was measured by ELISA.
Main Results:
- MeP modulated ERα expression but not ERβ.
- MeP activated the IKKα/β-dependent NF-κB pathway, yet ERs inhibited p65 NF-κB nuclear translocation.
- MeP reduced iNOS-dependent NO production but did not affect IL-8 secretion.
Conclusions:
- MeP influences human neutrophil function through modulation of intracellular signaling pathways.
- The study highlights the interplay between estrogen receptors and the NF-κB pathway in response to MeP exposure.
- MeP's effects on neutrophils suggest potential implications for immune function and health.
