Immunomodulatory effects of Bisphenol A, perfluorooctanoic acid, and tris(1,3-dichloro-2-propyl) phosphate on THP-1-derived macrophages.

Identifier:  imarina:9577471

Handle: https://hdl.handle.net/20.500.11797/imarina9577471

Authors:  Sabuz O; Blanco J; Deepika D; Schuhmacher M; Kumar V

Abstract:
Endocrine-disrupting chemicals (EDCs) are widespread environmental contaminants known to interfere with hormonal and immune functions. Among these, Bisphenol A (BPA), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and perfluorooctanoic acid (PFOA) are of significant concern due to their widespread human exposure and differing physicochemical profiles. Given that macrophages can represent early immune targets following EDC exposure, this study investigated the immunomodulatory effects of these structurally diverse compounds on THP-1-derived macrophage-like model. Cell viability was evaluated following 24 h exposure to a range of concentrations (1-100 µM), from which three doses (10, 50, 100 µM) were selected for functional assays. A follow-up viability assay at 48 h was performed to confirm the cellular impact of prolonged exposure. BPA and PFOA showed limited effects on cell viability, whereas TDCPP produced the most pronounced reduction. To assess immunomodulation, NFκB phosphorylation and cytokine production were evaluated under basal and LPS-stimulated conditions. BPA showed minimal effects across endpoints. TDCPP elicited modest NFκB activation, and under LPS stimulation, selectively attenuated specific cytokine responses. PFOA induced robust NFκB activation without corresponding changes in the measured cytokines, suggesting dissociation between upstream NFκB signaling and cytokine output in this model. Overall, these findings indicate compound-specific effects of BPA, TDCPP and PFOA in THP-1-derived macrophage-like cells and support the utility to this in vitro platform for comparative immunotoxicity screening and hypothesis generation. Future work integrating such data with quantitative in vitro-to-in vivo extrapolation (QIVIVIE/IVIVE) and more complex immune models may further improve human relevance.