Toxicology Letters 148 (2004) 95–102 The role of nitric oxide in the particulate matter (PM2.5)-induced NFB activation in lung epithelial cells Hae Yun Nam a,1 , Byung Hyune Choi b,1 , Joo Yong Lee b , Seok Geon Lee b , Young Hoon Kim b , Kweon Haeng Lee b,c , Hyoung Kyu Yoon d , Jeong Sup Song d , Hyung Jung Kim e , Young Lim a,∗ a Department of Occupational and Environmental Medicine, St. Mary’s Hospital, The Catholic University of Korea, Seoul 150-713, South Korea b Catholic Neuroscience Center, The Catholic University of Korea, Seoul 137-701, South Korea c Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea d Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea e Department of Internal Medicine, College of Medicine, Yonsei University, Seoul 120-7522, South Korea Received 8 September 2003; received in revised form 10 December 2003; accepted 11 December 2003 Abstract NFB 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 NFB activation were examined in A549 lung epithelial cells. NFB activation by 2.5 m particulates (PM2.5) was evident from the degradation of an NFB inhibitory protein, IB, and a luciferase reporter assay for NFB 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-N 6 -1-iminoethyl-lysine (L-NIL) clearly inhibited the NFB 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 NFB activity via the pathways involving ROS and/or RNS generation. Considering the fact that NFB also induces NO generation via iNOS expression, they might make a positive feedback loop that amplifies the downstream responses. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Particulate matter; Nuclear factor B; Nitric oxides; Inducible nitric oxide synthase ∗ Corresponding author. Tel.: +82-2-3779-1401; fax: +82-2-782-6017. E-mail address: nglim@catholic.ac.kr (Y. Lim). 1 The first two authors contributed equally to this work. 1. Introduction Epidemiological evidence suggests that there is a strong relationship between elevated particulate matter (PM) levels in urban environments and the increased incidence of morbidity and mortality due to the respi- ratory and/or cardiovascular diseases (Bascom et al., 1996; USEPA, 1996). This association appears to be 0378-4274/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.toxlet.2003.12.007