論文 - 詳細
| RRC ID | 85218 |
|---|---|
| 著者 | Anggraeni N, Vuong CK, Silvia P, Fukushige M, Yamashita T, Obata-Yasuoka M, Hamada H, Ohneda O. |
| タイトル | Mesenchymal stem cell-derived extracellular vesicles reduce inflammatory responses to SARS-CoV-2 and Influenza viral proteins via miR-146a/NF-κB pathway. |
| ジャーナル | Sci Rep |
| Abstract |
The risk of severe disease caused by co-infection with SARS-CoV-2 and influenza virus (IAV) raises an annual concern for global public health. Extracellular vesicles (EV) derived from mesenchymal stem cells (MSC) possess anti-inflammatory properties that can attenuate the inflammatory cytokine levels induced by viral infection. However, the effects of MSC-EV treatment on SARS-CoV-2 and IAV co-infection have not been elucidated. In the present study, we co-induced lung epithelial cells (EpiC) with SARS-CoV-2 Spike protein (S) and H1N1 influenza viral HA protein (HA) and found robust upregulation of inflammatory cytokines in comparison to those induced by either S or HA protein. Consequently, treatment of lung endothelial cells (EC) with conditioned medium from EpiC co-induced by both S and HA proteins resulted in increased apoptosis and impaired angiogenic ability, suggesting the effects of co-induction on epithelial-endothelial crosstalk. In addition, lung EpiC co-induced by both S and HA proteins showed paracrine effects on the recruitment of immune cells, including monocytes, macrophages and neutrophils. Of Note, EV derived from Wharton Jelly's MSC (WJ-EV) transferred miR-146a to recipient lung EpiC, which impaired TRAF6 and IRAK1, resulting in the downregulation of NF-κB pathway and secretion of inflammatory cytokines, rescuing the epithelial-endothelial crosstalk, and reducing the elevation of immune cell recruitment. Moreover, the anti-inflammatory properties of WJ-EV are affected by type 2 Diabetes Mellitus. WJ-EV derived from donors with type 2 Diabetes Mellitus contained less miR-146a and showed impaired ability to downregulate the NF-κB pathway and inflammatory cytokines in recipient cells. Taken together, our findings demonstrate the role of miR-146a in targeting the NF-κB pathway in the anti-inflammatory abilities of WJ-EV, which is a promising strategy to rescue the epithelial-endothelial crosstalk altered by co-infection with SARS-CoV-2 and IAV. |
| 巻・号 | 14(1) |
| ページ | 26649 |
| 公開日 | 2024-11-4 |
| DOI | 10.1038/s41598-024-77258-0 |
| PII | 10.1038/s41598-024-77258-0 |
| PMID | 39496662 |
| PMC | PMC11535355 |
| MeSH | COVID-19* / immunology COVID-19* / metabolism Cytokines / metabolism Endothelial Cells / metabolism Epithelial Cells / metabolism Epithelial Cells / virology Extracellular Vesicles* / metabolism Humans Inflammation / metabolism Inflammation / pathology Influenza A Virus, H1N1 Subtype* / physiology Influenza, Human / immunology Influenza, Human / metabolism Mesenchymal Stem Cells* / metabolism MicroRNAs* / genetics MicroRNAs* / metabolism NF-kappa B* / metabolism SARS-CoV-2* Signal Transduction* |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1 |