Oxidant Stress Incites Spreading of Macrophages via Extracellular Signal-Regulated Kinases and p38 Mitogen-Activated Protein Kinase

摘要: Cultured macrophages exhibit spreading in response to external stimuli. It is relevant vivo morphologic changes of during extravasation, migration, and differentiation. The present study was performed elucidate molecular mechanisms that regulate macrophages. Redox a crucial factor modulates wide range cell function. We found undergo oxidant stress caused by hydrogen peroxide or an generating agent menadione. To identify signaling pathways involved, role mitogen-activated protein (MAP) kinases investigated. Western blot analysis showed treatment with menadione rapidly induced phosphorylation extracellular signal-regulated (ERK1, ERK2) p38 MAP kinase, but not c-Jun N-terminal kinase (JNK). Pharmacologic inhibition either ERK activation blunted the macrophage spreading. Similarly, transfection dominant-negative mutants ERKs mutant significantly suppressed oxidant-triggered are known activate serum element (SRE) via ternary complex Elk-1. further downstream events, we focused on SRE. Stimulation Intervention SRE Elk-1 inhibited menadione-induced These results suggest oxygen radical metabolites, well-known mediators for tissue injury, incite kinase-SRE pathways.