Mitochondrial density contributes to the immune response of macrophages to lipopolysaccharide via the MAPK pathway

We investigated the role of mitochondrial reactive oxygen species (ROS) in the response of macrophages to lipopolysaccharide (LPS) using RAW 264.7 cells and their rho(0) cells lacking mitochondria. Mitochondrial density, respiratory activity and related proteins in rho(0) cells were significantly lower than those in RAW cells. LPS rapidly stimulated mitochondrial ROS prior to cytokine secretion, such as TNF-alpha and IL-6, from RAW 264.7 cells by activating the MAPK pathway, while the response was attenuated in rho(0) cells. Exposure of rho(0) cells to H(2)O(2) partially restored the secretion of cytokines induced by LPS. These results suggest that mitochondrial density and/or the respiratory state contribute to intracellular oxidative stress, which is responsible for the stimulation of LPS-induced MAPK signaling to enhance cytokine release from macrophages. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.