دورية أكاديمية
Pioglitazone Attenuates the Effects of Peripheral Inflammation in a Human In Vitro Blood–Brain Barrier Model
| العنوان: | Pioglitazone Attenuates the Effects of Peripheral Inflammation in a Human In Vitro Blood–Brain Barrier Model |
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| المؤلفون: | Gustavo Henrique Oliveira da Rocha, Rodrigo Azevedo Loiola, Marina de Paula-Silva, Fumitaka Shimizu, Takashi Kanda, Andrea Vieira, Fabien Gosselet, Sandra Helena Poliselli Farsky |
| المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 21, p 12781 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | blood–brain barrier, pioglitazone, peripheral inflammation, inflammatory bowel disease, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| العلاقة: | https://www.mdpi.com/1422-0067/23/21/12781Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms232112781 |
| الوصول الحر: | https://doaj.org/article/6ea02c76fbc44f349ca438d4524f06b4Test |
| رقم الانضمام: | edsdoj.6ea02c76fbc44f349ca438d4524f06b4 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms232112781 |