| Autor: |
da Rocha GHO; Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900, Brazil., Loiola RA; Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Faculté des Sciences Jean Perrin, Artois University, UR 2465, F-62300 Lens, France., de Paula-Silva M; Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900, Brazil., Shimizu F; Department of Neurology and Clinical Neuroscience, Yamaguchi University, Ube 755-8505, Japan., Kanda T; Department of Neurology and Clinical Neuroscience, Yamaguchi University, Ube 755-8505, Japan., Vieira A; Faculty of Medical Sciences, Clinic of Gastroenterology, Department of Medicine, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo 01221-020, Brazil., Gosselet F; Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Faculté des Sciences Jean Perrin, Artois University, UR 2465, F-62300 Lens, France., Farsky SHP; Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900, Brazil. |
| Abstrakt: |
Biological mediators secreted during peripheral chronic inflammation reach the bloodstream 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 pathways and mechanisms of injury at the BBB. We here employed a human in vitro BBB model to investigate the effects of either plasma from inflammatory bowel disease (IBD) patients or tumor necrosis 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/mL TNFα, 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 were attenuated by pioglitazone. Plasma from IBD patients, which evoked higher BBB permeability, also increased ICAM-1 expression, this effect being reversed by pioglitazone. Our findings evidence how pioglitazone controls periphery-elicited BBB inflammation and supports its repurposing for prevention/treating of such inflammatory conditions. |
