論文 - 詳細
| RRC ID | 72637 |
|---|---|
| 著者 | Franco-Trepat E, Guillán-Fresco M, Alonso-Pérez A, López-Fagúndez M, Pazos-Pérez A, Crespo-Golmar A, Gualillo O, Jorge-Mora A, Bravo SB, Gómez R. |
| タイトル | Repurposing drugs to inhibit innate immune responses associated with TLR4, IL1, and NLRP3 signaling in joint cells. |
| ジャーナル | Biomed Pharmacother |
| Abstract |
Osteoarthritis (OA) affects more than 300 million people worldwide and it is about to become the first disabling disease. OA is characterized by the progressive degradation of the articular cartilage but is a disease of the whole joint. Articular innate immune responses (IIR) associated with tissue degradation contribute to its progression. However, no treatment is available to block these IIRs. Through data text mining and computational pharmacology, we identified two clinical available drugs, naloxone, and thalidomide, with potential inhibitory properties on toll-like receptor 4 (TLR4), a major activator of these IIR. Proteome analysis confirmed that activation of this receptor or the IL1 receptor generated OA-like and gout-like proteomic changes in human primary chondrocytes. Both compounds were found to block TLR4 complex and inhibit TLR4 and IL1R-mediated IIR in OA chondrocytes, osteoblasts, and synoviocytes. Furthermore, naloxone and thalidomide inhibitory effects involved the downregulation of the NLRP3 inflammasome pathway, which is downstream of TLR4/IL1R signaling. We demonstrated that these compounds, within a therapeutic range of concentrations, exhibited anti-inflammatory and anti-catabolic properties in joint primary OA cells without any toxic effect. This data underpins naloxone & thalidomide repurpose to treat OA-associated inflammatory responses. |
| 巻・号 | 155 |
| ページ | 113671 |
| 公開日 | 2022-11-1 |
| DOI | 10.1016/j.biopha.2022.113671 |
| PII | S0753-3322(22)01060-5 |
| PMID | 36108390 |
| MeSH | Chondrocytes / metabolism Drug Repositioning Humans Immunity, Innate Inflammasomes / metabolism Interleukin-1 / metabolism NLR Family, Pyrin Domain-Containing 3 Protein / metabolism Naloxone / pharmacology Osteoarthritis* / metabolism Proteome / metabolism Proteomics Receptors, Interleukin-1 / metabolism Thalidomide / pharmacology Toll-Like Receptor 4* / metabolism |
| IF | 4.545 |
| 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 | 0.2 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |