The role of nitric oxide in the particulate matter (PM2.5)-induced NFκB activation in lung epithelial cells

Abstract

NFκB is one of key transcription factors that are involved in the inflammatory responses to the particulate matter (PM) in the lungs. In order to further understand the molecular mechanism, the effects of antioxidants and an inducible nitric oxide synthase (iNOS) inhibitor on PM-induced NFκB activation were examined in A549 lung epithelial cells. NFκB activation by 2.5 μm particulates (PM2.5) was evident from the degradation of an NFκB inhibitory protein, IκBα, and a luciferase reporter assay for NFκB activity. In these experiments, a pre-treatment of the cells with antioxidants N-acetyl-l-cysteine (NAC) and dimethylthiourea (DMTU) or an iNOS inhibitor l-N6-1-iminoethyl-lysine (L-NIL) clearly inhibited the NFκB activation by PM2.5. The inhibitory effect of L-NIL was also observed on the PM2.5-induced interleukin-8 (IL-8) gene expression both at the transcriptional and protein levels. These results suggest that PM2.5 induces NFκB activity via the pathways involving ROS and/or RNS generation. Considering the fact that NFκB also induces NO generation via iNOS expression, they might make a positive feedback loop that amplifies the downstream responses.