摘要：Background：Inhibition of pho sphodiesterase 4 （PDE4） improves the learning and memory abilities in Alzheimer’s disease animal models. The cognition-enhancing effects of PDE4 inhibition involve reduced inflammatory responses in the brain. However，the underlying mechanisms are ill-understood. cAMP induces autophagy，and defi ciency of autophagy leads to elevated inflammatory factors. In the present study，we aimed to investigate the contribution of autophagy to the anti-inflammatory effect of PDE4 inhibitor ROF. Methods：Acidic vesicles were traced by Lysotracker（ LYT） red and acridine orange（ AO） staining. Autophagosomes in BV-2 cells was observed by immunofluorescence staining of microtubule-associated protein 1 light chain 3 （LC3）. Aβ25-35 or lipopolysaccharide （LPS） with ATP were used to activate microglial cells and infl ammasome. Cytokine levels were measured by ELISA method. The levels of pro-infl ammatory factors and essential proteins involved in the formation of autophagosome were detected by Western blotting. Results：ROF increased the level of LC3-II，while the level of p62 was decreased. Enhanced fl uorescent signals were observed in BV-2 cells treated with ROF by AO and LYT red staining. In addition，immunofl uorescence indicated a signifi cant increase in punctate LC3. Both LPS plus ATP and Aβ25-35 enhanced the conversion of procaspase- 1 to cleaved-caspase-1 and increased the production of mature IL-1β. Interestingly，these effects were blocked by the treatment of ROF. Moreover，ROF decreased the apoptosis of neuronal N2a cells in conditioned media from BV-2 microglia. These effects were reversed by inhibition of microglial autophagy. Treatment with ROF also showed enhanced autophagy in mcie treated with LPS. Conclusions：PDE4 inhibitor ROF inhibits infl ammasome activities and reduces the release of IL-1β by inducing autophagy.