Platonin Inhibits Endotoxin-Induced MAPK and AP-1 Up-Regulation

Abstract

We previously have shown that platonin, a potent antioxidant, significantly attenuated inflammatory molecules up-regulation in RAW264.7 cells, a murine macrophage-like cell line. Inflammatory molecules expression is under the regulation of activator protein-1 (AP-1), a crucial transcription factor and a heterodimeric protein that composes of proteins from c-Jun and c-Fos families. AP-1 expression is regulated by mitogen-activated protein kinases (MAPKs). We sought to elucidate the effects of platonin on MAPKs and AP-1 up-regulation in activated RAW264.7 cells. RAW264.7 cells were allocated to receive phosphate buffered saline, lipopolysaccharide (LPS, 100 ng/mL), platonin (100 μM), or platonin plus LPS and designated as the PBS, LPS, platonin, or LPS + platonin group, respectively. After harvesting, expression of the investigated molecules was evaluated. The cytosolic protein concentrations of MAPKs, including extracellular regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK, of the LPS group were significantly higher than those of the PBS and platonin groups. The nuclear protein concentrations of AP-1, including c-Jun and c-Fos, and the AP-1-DNA binding activity of the LPS group were also significantly higher than those of the PBS and platonin groups. In contrast, the concentrations of ERK, JNK, and p38 MAPK of the LPS + platonin group were significantly lower than those of the LPS group. Moreover, the concentrations of c-Jun and c-Fos and the AP-1-DNA binding activity of the LPS + platonin group were significantly lower than those of the LPS group. Platonin significantly attenuated MAPKs and AP-1 upregulation in activated RAW264.7 cells.