LPS-induced autophagy is mediated by nitric oxide in macrophages (P1285)

Abstract

Abstract Activation of macrophages is essential for the host defense system and accumulating evidence suggests that autophagy is an important component of macrophage activity. Lipopolysaccharide activates Toll-like receptor 4 leading to the release of pro-inflammatory cytokines and inflammatory mediators, which are necessary to activate innate immune response. Another downstream response to LPS/TLR4 signaling is the induction of autophagy, but the signal transduction pathway leading to autophagy is unclear. Here we demonstrate that nitric oxide, which is induced by LPS, induces autophagy via a number of mechanisms in macrophages. To verify the role of NO in autophagy, we compared autophagy-related gene expression in LPS-stimulated and SNP-stimulated macrophages by western blotting. Both LPS and SNP stimulate autophagy in macrophages. In addition, inhibition of NO production by NOS inhibitors, L-NMMA and SMT, significantly reduced LPS-induced autophagy. These finding imply that LPS-induced autophagy might be mediated via NO production. The inhibition of MAPK or NF-κB by pharmacological inhibitors also impaired activation of autophagy by LPS in macrophages. Overall, these finding indicate that LPS induces autophagy in macrophages via activating MAPK/NF-κB/iNOS signaling pathway.