| Autor: |
Oliver, Paula M., Neubert, Patrick, Homann, Arne, Wendelborn, David, Bär, Anna-Lorena, Krampert, Luka, Trum, Maximilian, Schröder, Agnes, Ebner, Stefan, Weichselbaum, Andrea, Schatz, Valentin, Linz, Peter, Veelken, Roland, Schulte-Schrepping, Jonas, Aschenbrenner, Anna C., Quast, Thomas, Kurts, Christian, Geisberger, Sabrina, Kunzelmann, Karl, Hammer, Karin, Binger, Katrina J., Titze, Jens, Müller, Dominik N., Kolanus, Waldemar, Schultze, Joachim L., Wagner, Stefan, Jantsch, Jonathan |
| Rok vydání: |
2020 |
| Předmět: |
|
| DOI: |
10.5283/epub.44150 |
| Popis: |
Inflammation and infection can trigger local tissue Na(+)accumulation. This Na+-rich environment boosts proinflammatory activation of monocyte/macrophage-like cells (M phi s) and their antimicrobial activity. Enhanced Na+-driven M phi function requires the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5), which augments nitric oxide (NO) production and contributes to increased autophagy. However, the mechanism of Na(+)sensing in M phi s remained unclear. High extracellular Na(+)levels (high salt [HS]) trigger a substantial Na(+)influx and Ca(2+)loss. Here, we show that the Na+/Ca(2+)exchanger 1 (NCX1, also known as solute carrier family 8 member A1 [SLC8A1]) plays a critical role in HS-triggered Na(+)influx, concomitant Ca(2+)efflux, and subsequent augmented NFAT5 accumulation. Moreover, interfering with NCX1 activity impairs HS-boosted inflammatory signaling, infection-triggered autolysosome formation, and subsequent antibacterial activity. Taken together, this demonstrates that NCX1 is able to sense Na(+)and is required for amplifying inflammatory and antimicrobial M phi responses upon HS exposure. Manipulating NCX1 offers a new strategy to regulate M phi function. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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