論文 - 詳細
| RRC ID | 78292 |
|---|---|
| 著者 | Hu X, Zou M, Zheng W, Zhu M, Hou Q, Gao H, Zhang X, Liu Y, Cheng Z. |
| タイトル | Bhlhe40 deficiency attenuates LPS-induced acute lung injury through preventing macrophage pyroptosis. |
| ジャーナル | Respir Res |
| Abstract |
BACKGROUND:Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. Recently, increasing evidence supports activated inflammation and gasdermin D (GSDMD)-mediated pyroptosis in macrophage are closely associated with ALI. Basic helix-loop-helix family member e40 (Bhlhe40) is a transcription factor that is comprehensively involved in inflammation. However, there is little experimental evidence connecting Bhlhe40 and GSDMD-driven pyroptosis. The study sought to verify the hypothesis that Bhlhe40 is required for GSDMD-mediated pyroptosis in lipopolysaccharide (LPS)-induced inflammatory injury. METHOD:We performed studies using Bhlhe40-knockout (Bhlhe40 -/-) mice, small interfering RNA (siRNA) targeting Bhlhe40 and pyroptosis inhibitor disulfiram to investigate the potential roles of Bhlhe40 on LPS-induced ALI and the underlying mechanisms. RESULTS:Bhlhe40 was highly expressed in total lung tissues and macrophages of LPS-induced mice. Bhlhe40-/- mice showed alleviative lung pathological injury and inflammatory response upon LPS stimulation. Meanwhile, we found that Bhlhe40 deficiency significantly suppressed GSDMD-mediated pyroptosis in macrophage in vivo and in vitro. By further mechanistic analysis, we demonstrated that Bhlhe40 deficiency inhibited GSDMD-mediated pyroptosis and subsequent ALI by repressing canonical (caspase-1-mediated) and non-canonical (caspase-11-mediated) signaling pathways in vivo and in vitro. CONCLUSION:These results indicate Bhlhe40 is required for LPS-induced ALI. Bhlhe40 deficiency can inhibit GSDMD-mediated pyroptosis and therefore alleviate ALI. Targeting Bhlhe40 may be a potential therapeutic strategy for LPS-induced ALI. |
| 巻・号 | 25(1) |
| ページ | 100 |
| 公開日 | 2024-2-24 |
| DOI | 10.1186/s12931-024-02740-2 |
| PII | 10.1186/s12931-024-02740-2 |
| PMID | 38402153 |
| PMC | PMC10894472 |
| MeSH | Acute Lung Injury* / chemically induced Acute Lung Injury* / metabolism Acute Lung Injury* / prevention & control Animals Basic Helix-Loop-Helix Transcription Factors Caspases / adverse effects Homeodomain Proteins / adverse effects Inflammation Lipopolysaccharides* / toxicity Macrophages / metabolism Mice Pyroptosis RNA, Small Interfering |
| リソース情報 | |
| 実験動物マウス | RBRC04841 |