論文 - 詳細
| RRC ID | 83764 |
|---|---|
| 著者 | Cobo I, Murillo-Saich J, Alishala M, Calderon S, Coras R, Hemming B, Inkum F, Rosas F, Takei R, Spann N, Prohaska TA, Alabarse PVG, Jeong SJ, Nickl CK, Cheng A, Li B, Vogel A, Weichhart T, Fuster JJ, Le T, Bradstreet TR, Webber AM, Edelson BT, Razani B, Ebert BL, Taneja R, Terkeltaub R, Bryan RL, Guma M, Glass CK. |
| タイトル | Particle uptake by macrophages triggers bifurcated transcriptional pathways that differentially regulate inflammation and lysosomal gene expression. |
| ジャーナル | Immunity |
| Abstract |
Exposure to particles is a driver of several inflammatory diseases. Here, we investigated macrophage responses to monosodium urate crystals, calcium pyrophosphate crystals, aluminum salts, and silica nanoparticles. While each particle induced a distinct gene expression pattern, we identified a common inflammatory signature and acute activation of lysosomal acidification genes. Using monosodium urate crystals as a model, we demonstrated that this lysosomal gene program is regulated by a 5'-prime-AMP-activated protein kinase (AMPK)-dependent transcriptional network, including TFEB, TFE3, and the epigenetic regulators DNA methyl transferase 3a (DNMT3A) and DOT1L. This lysosomal acidification program operates in parallel with, but largely independently of, a JNK-AP-1-dependent network driving crystal-induced chemokine and cytokine expression. These findings reveal a bifurcation in pathways governing inflammatory and lysosomal responses, offering insights for treating particle-associated diseases. |
| 巻・号 | 58(4) |
| ページ | 826-842.e8 |
| 公開日 | 2025-4-8 |
| DOI | 10.1016/j.immuni.2025.02.023 |
| PII | S1074-7613(25)00090-1 |
| PMID | 40118070 |
| MeSH | AMP-Activated Protein Kinases / metabolism Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism DNA Methyltransferase 3A Gene Expression Regulation Humans Inflammation* / genetics Inflammation* / immunology Inflammation* / metabolism Lysosomes* / genetics Lysosomes* / metabolism Macrophages* / immunology Macrophages* / metabolism Mice Nanoparticles Signal Transduction Silicon Dioxide Transcription, Genetic Uric Acid |
| IF | 22.553 |
| 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 | 51 |
| 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 | |
| 実験動物マウス | RBRC03731 |