Pioglitazone Attenuates the Effects of Peripheral Inflammation in a Human In Vitro Blood–Brain Barrier Model

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da Rocha, Gustavo, Henrique Oliveira | Loiola, Rodrigo, Azevedo | de Paula-Silva, Marina | Shimizu, Fumitaka | Kanda, Takashi | Vieira, Andrea | Gosselet, Fabien | Farsky, Sandra, Helena Poliselli

Edité par CCSD ; MDPI -

International audience. Biological mediators secreted during peripheral chronic inflammation reach the blood-stream and may damage the blood–brain barrier (BBB), triggering central nervous system (CNS)disorders. Full-fledged human BBB models are efficient tools to investigate pharmacological path-ways and mechanisms of injury at the BBB. We here employed a human in vitro BBB model toinvestigate the effects of either plasma from inflammatory bowel disease (IBD) patients or tumornecrosis factor α (TNFα), a cytokine commonly released in periphery during IBD, and the anti-inflammatory role of pioglitazone, a peroxisome proliferator-activated receptor γ agonist (PPARγ).The BBB model was treated with either 10% plasma from healthy and IBD donors or 5 ng/mLTNFα, following treatment with 10 µM pioglitazone. Patient plasma did not alter BBB parameters,but TNFα levels in plasma from all donors were associated with varying expression of claudin-5,claudin-3 and ICAM-1. TNFα treatment increased BBB permeability, claudin-5 disarrangement,VCAM-1 and ICAM-1 expression, MCP1 secretion and monocyte transmigration. These effects wereattenuated by pioglitazone. Plasma from IBD patients, which evoked higher BBB permeability, alsoincreased ICAM-1 expression, this effect being reversed by pioglitazone. Our findings evidencehow pioglitazone controls periphery-elicited BBB inflammation and supports its repurposing forprevention/treating of such inflammatory conditions.

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