Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants that are added to numerous products to prevent accidental fires. Even though there is little information on the health effects of PBDE exposure, it is still of concern to humans because some types of PBDEs can build up in the fatty tissues of the several aquatic and terrestrial animals entering the food chain (EFSA Panel, 2011). A few surveys demonstrated that PBDEs bioaccumulate in human tissues with particular attention to human milk. Recently, their presence has been correlated to several pathologies but little is known about their effect on the human innate immune system activity. In this study we investigated the effect of the congener 2,2',4,4'- Tetrabromodiphenyl ether (PBDE-47) on the functional activity of the THP-1 human macrophages cell line and on ex vivo freshly isolated human basophils. Cytotoxicity and genotoxicity studies showed that PBDE-47 was able to induce toxic effects on the THP-1 cell line viability at concentrations >=25 µM. Immune function of THP1 was studied after stimulation with bacterial lipopolysaccharide (LPS) and PBDE-47 exposure at concentrations granting macrophage viability. Two dimensional electrophoresis showed modification of the proteome in the 3 µM PBDE-47 treated sample and Real Time PCR and ELISA demonstrated a statistically significant reduction in the expression of IL-1?, IL-6 and TNF-? cytokines. Furthermore, PBDE-47 was able to perturbate genes involved in cell motility upregulating CDH-1 and downregulating 38 MMP-12 expressions. Finally, basophil activation assay showed reduced CD63 activation in PBDE-47 treated samples. In conclusion, our study demonstrated that PBDE-47 may perturb the activities of cells involved in innate immunity dampening the expression of macrophage proinflammatory cytokines (IL-1?, IL-6 and TNF-?) and genes involved in cell motility (MMP-12 and E-cadherin) and interfering with basophil activation suggesting that this compound can impair innate immune response.
In vitro exposure to 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) impairs innate inflammatory response
Valeria Longo;Caterina Di Sano;Diego Cigna;Fabio Cibella;Paolo Colombo
2019
Abstract
Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants that are added to numerous products to prevent accidental fires. Even though there is little information on the health effects of PBDE exposure, it is still of concern to humans because some types of PBDEs can build up in the fatty tissues of the several aquatic and terrestrial animals entering the food chain (EFSA Panel, 2011). A few surveys demonstrated that PBDEs bioaccumulate in human tissues with particular attention to human milk. Recently, their presence has been correlated to several pathologies but little is known about their effect on the human innate immune system activity. In this study we investigated the effect of the congener 2,2',4,4'- Tetrabromodiphenyl ether (PBDE-47) on the functional activity of the THP-1 human macrophages cell line and on ex vivo freshly isolated human basophils. Cytotoxicity and genotoxicity studies showed that PBDE-47 was able to induce toxic effects on the THP-1 cell line viability at concentrations >=25 µM. Immune function of THP1 was studied after stimulation with bacterial lipopolysaccharide (LPS) and PBDE-47 exposure at concentrations granting macrophage viability. Two dimensional electrophoresis showed modification of the proteome in the 3 µM PBDE-47 treated sample and Real Time PCR and ELISA demonstrated a statistically significant reduction in the expression of IL-1?, IL-6 and TNF-? cytokines. Furthermore, PBDE-47 was able to perturbate genes involved in cell motility upregulating CDH-1 and downregulating 38 MMP-12 expressions. Finally, basophil activation assay showed reduced CD63 activation in PBDE-47 treated samples. In conclusion, our study demonstrated that PBDE-47 may perturb the activities of cells involved in innate immunity dampening the expression of macrophage proinflammatory cytokines (IL-1?, IL-6 and TNF-?) and genes involved in cell motility (MMP-12 and E-cadherin) and interfering with basophil activation suggesting that this compound can impair innate immune response.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
