Aryl hydrocarbon receptor upregulates IL-1 beta expression in hCMEC/D3 human cerebral microvascular endothelial cells after TCDD exposure

作者：Jacob Aude; Tomkiewicz Raulet Celine; Jamet Charlotte; Bendayan Reina; Massicot France; Coumoul Xavier; Decleves Xavier

来源：Toxicology in Vitro, 2017, 41: 200-204.

DOI：10.1016/j.tiv.2017.03.001

• Aryl hydrocarbon receptor
• Blood-brain barrier
• hCMEC/D3
• Pro-inflammatory cytokines

The AhR is a cytosolic ligand-dependent transcription factor activated by both endogenous and exogenous chemicals. It can regulate expression of many target genes including some inflammatory cytokines and chemokines. To date AhR implication in the regulation of inflammatory cytokines and chemokines at human cerebral endothelium has not been addressed. In the present study, we investigated whether AhR could regulate the expression of two pro-inflammatory cytokines and one chemokine i.e. IL-1 beta, IL-6 and IL-8 in the hCMEC/D3 human cerebral microvascular endothelial cell line. Exposure to TCDD increased IL-1 beta mRNA expression levels in hCMEC/D3. By using small interfering RNA against AhR we demonstrated that TCDD effects on IL-1 beta expression were mediated through AhR activation. Regarding IL-6 and IL-8, TCDD exposure had little or no effect on their mRNA levels in hCMEC/D3. In conclusion, our findings suggest that AhR-mediated IL-1 beta regulation in cerebral endothelium could induce BBB breakdown and contribute to the pathogenesis of a variety of neurologic disorders.

• 出版日期2017-6