Matrix metalloproteinase-2 and -9 are induced differently by metal nanoparticles in human monocytes: The role of oxidative stress and protein tyrosine kinase activation

摘要: Recently, many studies have shown that nanoparticles can translocate from the lungs to circulatory system. As a particulate foreign body, could induce host responses such as reactive oxygen species (ROS) generation, inflammatory cytokine and matrix metalloproteinase (MMP) release which play major role in tissue destruction remodeling. However, direct effects of on leukocytes, especially monocytes, are still unclear. The objective present study was compare ability Nano-Co Nano-TiO2 cause alteration transcription activity MMPs explore possible mechanisms. We hypothesized non-toxic doses some transition metal stimulate an imbalance MMP/TIMP MMP production may contribute their health effects. To test this hypothesis, U937 cells were treated with cytotoxic ROS generation measured. MMP-2 MMP-9 expression after exposure these subsequently determined. investigate potential signaling pathways involved Nano-Co-induced activation, scavengers or inhibitors, AP-1 inhibitor, protein tyrosine kinase (PTK) inhibitors also used pre-treat cells. Our results demonstrated Nano-Co, but not Nano-TiO2, at dose does cytotoxicity, resulted up-regulation mRNA expression.. showed dose- time-related increases pro-MMP-2 pro-MMP-9 gelatinolytic activities conditioned media Nano-TiO2. inhibited by pre-treatment inhibitors. decreases metalloproteinases 2 (TIMP-2) neither nor led any transcriptional change TIMP-1. decrease TIMP-2 curcumin, PTK specific herbimycin A genistein, prior significantly abolished and-9 activity. suggest causes between is mediated due oxidative stress.