Abstract
Pentoxifylline (PTX), as a methylxanthine derivative and nonspecific phosphodiesterase inhibitor, has the characteristics of anti-inflammatory and partial inflammatory process inhibition. However, the regulatory effect of PTX on inflammatory cytokines is unclear. Autophagy can regulate the activation of inflammasomes and then inhibit inflammation as previously described. Our study attempts to explore the relationship between autophagy and PTX-mediated regulation of inflammasome suppression. Macrophage-like RAW264.7 cells were studied as the in vitro macrophage model. We investigated the anti-inflammatory effect caused by PTX with time and dose response against the LPS-induced inflammatory factors (TNF-α, IL-1β). Western blot detected the levels of autophagy-related proteins Beclin-1 and LC3, as well as the signal pathways of AMPK and p-AMPK. Fluorescence microscope and transmission electron microscope were used to observe the autophagy bodies in cells influenced by PTX. The autophagy in cells inhibited by PTX exhibited dose- and time-dependent effects, and PTX alleviated LPS-induced inflammation caused by retarded autophagy. Furthermore, in RAW264.7 macrophage cells, our data indicated that AMPK signaling perhaps functioned importantly in repressed autophagy. In addition, in RAW264.7 macrophages, our data suggested that AMPK signaling might play an important role in inhibiting autophagy during the process of PTX ameliorating LPS-mediated inflammation.