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BPA analogues affect intestinal barrier integrity and pro-inflammatory response in a coculture model
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Resumo(s)
Background: Bisphenol (BP) A and its structural analogues are environmental pollutants with endocrine-disrupting properties and potential immune-modulating effects. Following legal restrictions on the use of BPA, structurally related compounds including BPAP, BPP, and BPS-MAE have been introduced as alternatives; however, their potential hazardous profiles remain largely unknown. Here we used a coculture cell model to investigate the effects of exposure to these BP analogues on intestinal barrier integrity, intestinal cell stress, and pro-inflammatory macrophage activation.
Methods: As cellular model, Caco-2 cells were grown on filter membranes to a polarized epithelium-like layer, and cocultured with underlying basolateral THP-1 derived M0 macrophages. After apical exposure of the Caco-2 cells layer to BPs (0.1 -100 µM for 24 h), we determined transepithelial electrical resistance (TEER), polarized cell morphology by confocal microscopy, cellular stress markers (p-p38MAPK, p-JNK, p-eIF2α) by Western blot, and macrophage activation by IL-1β-transcript expression changes. In addition, M0-type macrophages were also directly incubated with BPA for comparison.
Results: When M0 macrophages were directly exposed, BPA triggered IL-1β expression, an effect more evident after macrophage sensitization by the presence of interferon-γ. Apical exposure to BPA and BPS-MAE had little effect on TEER but induced some increase in epithelial stress markers, while BPAP and especially BPP clearly reduced TEER and polarized cell morphology, and showed a tendency to induce stress markers. In addition, apical cell exposure to BPP and BPS-MAE triggered clear expression of the pro-inflammatory marker IL-1β in sensitized M0 macrophages cocultured at the basolateral side, whereas BPAP and BPA were only effective at the highest concentration.
Conclusion: Together, our data show that exposure of an intestinal epithelium-like layer to BPAP and BPS-MAE revealed adverse cellular effects similar to BPA, while BPP was clearly the most deleterious BP analogue. Pro-inflammatory macrophage activation was strongest after exposure to BPP followed by BPS-MAE.
Descrição
Palavras-chave
Vias de Transdução de Sinal e Patologias Associadas Caco-2 Intestinal Barrier Bisphenol Compound Inflammation
Contexto Educativo
Citação
Editora
Partnership for the Assessment of Risks from Chemicals (PARC)- WP5 annual meeting