Hydrogen peroxide induces the production of tumor necrosis factor-α in RAW 264.7 macrophage cells via activation of p38 and stress-activated protein kinase

Abstract

The effect of hydrogen peroxide (H2O2) on production of tumor necrosis factor (TNF)-α was examined in RAW 264.7 murine macrophage cells. H2O2 led to production of TNF-α up to 24 h after the treatment, but not nitric oxide in RAW 264.7 cells. H2O2 induced TNF-α production in mouse peritoneal macrophages as well as RAW 264.7 cells. The H2O2induced TNF-α production was prevented by inhibitors of p38 and stress-activated protein kinase (SAPK/ JNK), and H2O2 induced the phosphorylation of p38 and SAPK. Further, H2O2 significantly augmented the AP-1 activity, but not nuclear factor (NF)-κB activity in RAW 264.7 cells. A high level of intracellular reactive oxygen radicals (ROS) was detected in H2O2-exposed RAW 264.7 cells. Ebselen, a cell permeable antioxidant, prevented the H2 O2-induced TNFα production. H2 O2 significantly enhanced lipopolysaccharide (LPS)-induced TNF-α production. Therefore, H2O2 was suggested to induce TNF-α production in macrophages via activating p38 and SAPK/JNK as oxidative stress-related signal pathways. © SAGE Publications 2008.