Substance P mediates AP-1 induction in A549 cells via reactive oxygen species

Here, the role of SP on ROS induction and the downstream activation of AP-1 in A549 airway epithelial cells was investigated by dichloroflourescein-diacetate method and reporter gene assays. The SP-mediated AP-1 induction was dependent on extracellular calcium and ROS. The likely source of ROS are the mitochondria as rotenone inhibited AP-1 induction and the p47phox subunit of the NADPH oxidase complex, responsible for ROS generation in phagocytotic cells, was not expressed in A549 cells assayed by RT-PCR. This is consistent with results obtained from cells of murine bronchial epithelium, isolated by laser capture microdissection. In summary, this study provides evidence for an SP-mediated induction of AP-1, which may contribute to the expression of pro-inflammatory cytokines.