論文 - 詳細
| RRC ID | 51235 |
|---|---|
| 著者 | Kambara H, Liu F, Zhang X, Liu P, Bajrami B, Teng Y, Zhao L, Zhou S, Yu H, Zhou W, Silberstein LE, Cheng T, Han M, Xu Y, Luo HR. |
| タイトル | Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death. |
| ジャーナル | Cell Rep |
| Abstract |
Gasdermin D (GSDMD) is considered a proinflammatory factor that mediates pyroptosis in macrophages to protect hosts from intracellular bacteria. Here, we reveal that GSDMD deficiency paradoxically augmented host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, which established GSDMD as a negative regulator of innate immunity. In contrast to its activation in macrophages, in which activated inflammatory caspases cleave GSDMD to produce an N-terminal fragment (GSDMD-cNT) to trigger pyroptosis, GSDMD cleavage and activation in neutrophils was caspase independent. It was mediated by a neutrophil-specific serine protease, neutrophil elastase (ELANE), released from cytoplasmic granules into the cytosol in aging neutrophils. ELANE-mediated GSDMD cleavage was upstream of the caspase cleavage site and produced a fully active ELANE-derived NT fragment (GSDMD-eNT) that induced lytic cell death as efficiently as GSDMD-cNT. Thus, GSDMD is pleiotropic, exerting both pro- and anti-inflammatory effects that make it a potential target for antibacterial and anti-inflammatory therapies. |
| 巻・号 | 22(11) |
| ページ | 2924-2936 |
| 公開日 | 2018-3-13 |
| DOI | 10.1016/j.celrep.2018.02.067 |
| PII | S2211-1247(18)30261-4 |
| PMID | 29539421 |
| PMC | PMC5878047 |
| MeSH | Animals Anti-Inflammatory Agents / pharmacology Anti-Inflammatory Agents / therapeutic use* Apoptosis Regulatory Proteins / pharmacology Apoptosis Regulatory Proteins / therapeutic use* Cell Death / drug effects* Humans Intracellular Signaling Peptides and Proteins Mice Neutrophils / drug effects* Phosphate-Binding Proteins |
| IF | 8.109 |
| 引用数 | 51 |
| 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 | 16 |
| 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 | |
| 遺伝子材料 | CSII-EF-RfA (RDB04385) CSII-CMV-MCS-IRES2-Bsd (RDB04385). |