Background:Inhibition of phosphodiesterase 4(PDE4)improves the leing and memory abilities in Alzheimers 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 deficiency 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 inflammasome. Cytokine levels were measured by ELISA method. The levels of pro-inflammatory factors and essential proteins involved in the formation of autophagosome were detected by West blotting. Results:ROF increased the level of LC3-II,while the level of p62 was decreased. Enhanced fluorescent signals were observed in BV-2 cells treated with ROF by AO and LYT red staining. In addition,immunofluorescence indicated a significant increase in punctate LC3. Both LPS plus ATP and Aβ25-35 enhanced the conversion of pro-caspase-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 inflammasome activities and reduces the release of IL-1βby inducing autophagy.