Toll-Like Receptor 2 Ligation Enhances Therapeutic Effects of Mesenchymal Stem Cells on Murine Model of Asthmatic Inflammation
| Autor: | Hui-Chieh Yu, 俞惠潔 |
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| Rok vydání: | 2018 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 106 Under current therapeutic strategies, the cure to asthma remains elusive; thus- novel approaches for treating asthma are desperately needed. Despite that mesenchymal stem cells (MSCs) have recently been established as potential candidates by virtue of their immunomodulatory properties, the underlying heterogeneity of MSCs diminishes their therapeutic efficacy. Here we evaluated a toll-like receptor (TLR) 2 ligation protocol of MSCs to augment their therapeutic benefits on asthma. We surmise that more effective MSCs were activated with a TLR2 ligand, Pam3CSK4, at low concentration (1 μg/mL) for a longer period (96 h) induction prior to intravenous administration for ameliorating asthma in mice in a post-treatment manner. We further validated this regimen by demonstrating that Pam3CSK4 activated STAT3 in BM-MSCs through IL-6, which was likely stimulated with NF-κB signaling. Nitric oxide (NO), the key suppressive molecule of Pam3CSK4-primed BM-MSCs, was later highly increased through upregulation of iNOS, which was in the downstream of STAT3 phosphorylation. The intensified suppressive functions of BM-MSCs were then executed by inducing CD4+CD25+Foxp3+ regulatory T cells in a post-treatment manner. The consistent therapeutic outcomes and the valid suppressive mechanisms in the study might shed light on eliminating the proinflammation-prone uncertainties of MSCs, and enhancing the future feasibility of obtaining long-term effects with this regimen. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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