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In Vitro Effects of Bisphenol Analogs on Immune Cells Activation and Th Differentiation
Pia Štrukelj Pahović1,2, Martina Iulini2, Ambra Maddalon2
1Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Insights
Bisphenols like BPA, BPAF, and BPS can alter immune cell responses. These endocrine disruptors impact immune cell activation and cytokine release, confirming their potential immunotoxicity.
Area of Science:
- Immunotoxicology
- Endocrinology
- Cellular immunology
Background:
- Bisphenol A (BPA) is widely used, but analogues like BPAF and BPS are replacing it due to regulations.
- Emerging evidence suggests bisphenol analogues may pose similar or greater toxic and endocrine-disrupting risks compared to BPA.
- RACK1 expression links endocrine disruption to immunotoxicity; BPA/BPAF decrease it, while BPS increases it.
Purpose of the Study:
- To investigate the immunomodulatory effects of BPA, BPAF, and BPS.
- To examine cellular responses in THP-1 cells and peripheral blood mononuclear cells (PBMCs).
- To assess effects under lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) and ionomycin activation.
Main Methods:
- Utilized THP-1 cell line and human PBMCs.
- Activated immune cells using LPS stimulation.
- Activated immune cells using PMA and ionomycin stimulation.
Main Results:
- BPA and BPAF reduced LPS-induced surface marker expression and pro-inflammatory cytokine release.
- BPS enhanced LPS-induced CD86 and cytokine expression.
- All tested bisphenols influenced T helper cell differentiation and cytokine release, with some gender-related effects observed after PMA/ionomycin activation.
Conclusions:
- Bisphenols demonstrate the capacity to modulate immune cell differentiation and activation.
- These findings support the classification of bisphenols as potentially immunotoxic substances.
- The study highlights the need for caution regarding the safety of BPA alternatives.
Aims:
Investigate the immunomodulatory effects of bisphenols in the THP-1 cell line and peripheral blood mononuclear cells in response to lipopolysaccharide (LPS) activation or to phorbol 12-myristate 13-acetate (PMA) and ionomycin.
Background:
We have previously demonstrated the usefulness of the evaluation of RACK1 expression as a link between endocrine disrupting activity and the immunotoxic effect of xenobiotics. We demonstrated that while BPA and BPAF reduced RACK1 expression, BPS was able to increase it.
Objective:
Bisphenol A (BPA) is one of the most commonly used chemicals in the manufacturing of polycarbonate plastics and plastic consumer products. Its endocrine disrupting (ED) potential and changes in European regulations have led to replacing BPA in many uses with structurally similar chemicals, like bisphenol AF (BPAF) and bisphenol S (BPS). However, emerging data indicated that bisphenol analogues may not be safer than BPA both in toxic effects and ED potential.
Methods:
THP-1 cell line and peripheral blood mononuclear cells were activated with lipopolysaccharide (LPS) or with phorbol 12-myristate 13-acetate (PMA) and ionomycin.
Results:
BPA and BPAF decreased LPS-induced expression of surface markers and the release of pro-inflammatory cytokines, while BPS increased LPS-induced expression of CD86 and cytokines. BPA, BPAF, and BPS affected PMA/ionomycin-induced T helper differentiation and cytokine release with gender-related alterations in some parameters investigated.
Conclusion:
Data confirm that bisphenols can modulate immune cell differentiation and activation, further supporting their immunotoxic effects.
