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BPA analogues affect intestinal barrier integrity and pro-inflammatory response in a coculture model

datacite.subject.fosCiências Médicas
datacite.subject.sdg03:Saúde de Qualidade
dc.contributor.authorPereira, Gonçalo
dc.contributor.authorBarros, Patrícia
dc.contributor.authorMatos, Paulo
dc.contributor.authorJordan, Peter
dc.date.accessioned2026-03-04T14:46:32Z
dc.date.available2026-03-04T14:46:32Z
dc.date.issued2025-05-13
dc.description.abstractBackground: 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.eng
dc.description.sponsorshipThis work was carried out in the framework of the European Partnership for the Assessment of Risks from Chemicals (PARC) and has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014.
dc.identifier.urihttp://hdl.handle.net/10400.18/11128
dc.language.isoeng
dc.peerreviewedno
dc.publisherPartnership for the Assessment of Risks from Chemicals (PARC)- WP5 annual meeting
dc.relationPartnership for the Assessment of Risks from Chemicals
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectVias de Transdução de Sinal e Patologias Associadas
dc.subjectCaco-2
dc.subjectIntestinal Barrier
dc.subjectBisphenol Compound
dc.subjectInflammation
dc.titleBPA analogues affect intestinal barrier integrity and pro-inflammatory response in a coculture modeleng
dc.typeconference object
dspace.entity.typePublication
oaire.awardNumber101057014
oaire.awardTitlePartnership for the Assessment of Risks from Chemicals
oaire.awardURIhttp://hdl.handle.net/10400.18/10776
oaire.citation.conferenceDate2025-05
oaire.citation.conferencePlaceOslo, Norway
oaire.citation.titlePartnership for the Assessment of Risks from Chemicals (PARC) – WP5 Annual Meeting, 12-14 May 2025
oaire.fundingStreamHORIZON Programme Cofund Actions
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
relation.isProjectOfPublication87519d63-05e5-4a7a-9a69-893088bf7517
relation.isProjectOfPublication.latestForDiscovery87519d63-05e5-4a7a-9a69-893088bf7517

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