From the roundabout of molecular events to nanomaterial-induced chronic inflammation prediction
| Autor: | Olivier Joubert, Mojca Pušnik, Nick Quirke, Ulla Vogel, Iztok Urbančič, Sabina Halappanavar, Boštjan Kokot, Polona Umek, Pernille Høgh Danielsen, Stane Pajk, Lobaskin, Petra Čotar, López Cb, Patrycja Zawilska, Johannes Beckers, Otmar Schmid, Qiaoxia Zhou, T. Stoeger, Claudia Contini, Rok Podlipec, Ana Krišelj, Mikhail Ivanov, Trine Berthing, Hana Majaron, Jessica Ponti, Martin Irmler, Zahra Doumandji, Janez Štrancar, M. Schneemilch, Alexander P. Lyubartsev, Carola Voss, Zhernovkov, Aleksandar Sebastijanović, Tilen Koklic |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Single exposure Mechanism (biology) Chemistry In silico Inflammation Lipid metabolism 02 engineering and technology 021001 nanoscience & nanotechnology In vitro 3. Good health Cell biology Proinflammatory cytokine 03 medical and health sciences In vivo medicine medicine.symptom 0210 nano-technology 030304 developmental biology |
| Zdroj: | BioRxiv bioRxiv |
| ISSN: | 1943-0264 |
| DOI: | 10.1101/2020.02.27.966036 |
| Popis: | Many chronic diseases manifest in prolonged inflammation and often ignored dysregulated lipid metabolism. When associated with inhalation of nanomaterials, limited information is available on the relevant molecular events and their causal connections. This prevents reliable prediction of outcomes by efficient testing strategies. To unravel how acute nanomaterial exposure leads to chronic conditions, we employed advanced microscopy and omics in vitro and in vivo together with in silico modelling. For selected metal-oxide nanomaterials, we show that lung epithelial cells survive the exposure by excreting internalized nanomaterials and passivating them on the surface, employing elevated lipid synthesis. Macrophages, on the contrary, lose their integrity whilst degrading the passivized bio-nano agglomerates, releasing the nanomaterials, which are taken up again by the epithelial cells. Constant proinflammatory signalling recruits new phagocytes that feed the vicious cycle of events, resulting in a long-lasting response to a single exposure. The proposed mechanism explains the nanomaterial-associated in vivo chronic outcomes and allows its prediction based on in vitro measurements. Similar mechanisms may trigger other chronic diseases affecting millions of lives worldwide. |
| Databáze: | OpenAIRE |
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