| 초록 |
Hyper-inflammatory responses triggered by intracellular reactive oxygen species (ROS) can lead to a variety of diseases, including sepsis and colitis. In this study, we demonstrate that c-Src is a negative regulator of cellular ROS generation through its binding to p47phox. This molecule also competitively inhibits the NADPH oxidase complex (NOX) assembly. Further, we showed N8 peptide, an N-terminal 8-amino acid peptide derived from p22phox, was sufficient for Rubicon interaction and thus, capable of robustly blocking the Rubicon-p22phox interaction and profoundly suppressing ROS and inflammatory cytokine production. The SPG-SH3 peptide, Tat-N8 peptide or a N8 peptide-mimetic small molecule has a significant therapeutic effect on mouse ROS-mediated inflammatory disease models, cecal-ligation and puncture-induced sepsis and dextran sodium sulfate-induced colitis. Therefore, the host-defense peptide is a potential therapeutic agent for ROS-associated lethal inflammatory diseases. |
