| Status | 已發表Published |
| Roflupram, a Phosphodiesterase Inhibitior, Suppresses Inflammasome Activation through Autophagy in Microglial Cells | |
| Zheng, W. | |
| 2017-06-19 | |
| Source Publication | ACS chemical neuroscience
 |
| ISSN | 1948-7193 |
| Pages | 1-11 |
| Abstract | ABSTRACT: Inhibition of phosphodiesterase 4 (PDE4) 13 suppressed the inflammatory responses in the brain. However, 14 the underlying mechanisms are poorly understood. Roflupram 15 (ROF) is a novel PDE4 inhibitor. In the present study, we 16 found that ROF enhanced the level of microtubule-associated 17 protein 1 light chain 3 II (LC3-II) and decreased p62 in 18 microglial BV-2 cells. Enhanced fluorescent signals were 19 observed in BV-2 cells treated with ROF by Lysotracker red 20 and acridine orange staining. In addition, immunofluorescence 21 indicated a significant increase in punctate LC3. Moreover, β 22 amyloid 25−35 (Aβ25−35) or lipopolysaccharide (LPS) with ATP was used to activate inflammasome. We found that both LPS 23 plus ATP and Aβ25−35 enhanced the conversion of pro-caspase-1 to cleaved-caspase-1 and increased the production of mature IL- 24 1β in BV-2 cells. Interestingly, these effects were blocked by the treatment of ROF. Consistently, knocking down the expression 25 of PDE4B in primary microglial cells led to enhanced level of LC-3 II and decreased activation of inflammasome. What’s more, 26 Hoechst staining showed that ROF decreased the apoptosis of neuronal N2a cells in conditioned media from microglia. Our data 27 also showed that ROF dose-dependently enhanced autophagy, reduced the activation of inflammasome and suppressed the 28 production of IL-1β in mice injected with LPS. These effects were reversed by inhibition of microglial autophagy. These results 29 put together demonstrate that ROF inhibits inflammasome activities and reduces the release of IL-1β by inducing autophagy. 30 Therefore, ROF could be used as a potential therapeutic compound for the intervention of inflammation-associated diseases in 31 the brain. |
| Keyword | Phosphodiesterase 4 roflupram autophagy inflammasome microglia neuroinflammation |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 29962 |
| Document Type | Journal article |
| Collection | University of Macau |
| Recommended Citation GB/T 7714 | Zheng, W.. Roflupram, a Phosphodiesterase Inhibitior, Suppresses Inflammasome Activation through Autophagy in Microglial Cells[J]. ACS chemical neuroscience, 2017, 1-11. |
| APA | Zheng, W..(2017). Roflupram, a Phosphodiesterase Inhibitior, Suppresses Inflammasome Activation through Autophagy in Microglial Cells. ACS chemical neuroscience, 1-11. |
| MLA | Zheng, W.."Roflupram, a Phosphodiesterase Inhibitior, Suppresses Inflammasome Activation through Autophagy in Microglial Cells".ACS chemical neuroscience (2017):1-11. |
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