title: The role of nitric oxide in the particulate matter (PM2.5)-induced NFkappaB activation in lung epithelial cells.
abstract: NFkappaB 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 NFkappaB activation were examined in A549 lung epithelial cells. NFkappaB activation by 2.5 microm particulates (PM2.5) was evident from the degradation of an NFkappaB inhibitory protein, IkappaBalpha, and a luciferase reporter assay for NFkappaB 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 NFkappaB 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 NFkappaB activity via the pathways involving ROS and/or RNS generation. Considering the fact that NFkappaB also induces NO generation via iNOS expression, they might make a positive feedback loop that amplifies the downstream responses.
authors.affiliation: Department of Occupational and Environmental Medicine, St. Mary's Hospital, The Catholic University of Korea, Seoul 150-713, South Korea.
authors.forename: Hae Yun
authors.initials: HY
authors.lastname: Nam
authors.forename: Byung Hyune
authors.initials: BH
authors.lastname: Choi
authors.forename: Joo Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Seok Geon
authors.initials: SG
authors.lastname: Lee
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Kweon Haeng
authors.initials: KH
authors.lastname: Lee
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Yoon
authors.forename: Jeong Sup
authors.initials: JS
authors.lastname: Song
authors.forename: Hyung Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young
authors.initials: Y
authors.lastname: Lim
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D018929:Cell Culture Techniques; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000276:immunology / Q000473:pathology*; D016328:NF-kappa B / Q000494:pharmacology*; D009569:Nitric Oxide / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000494:pharmacology; D010316:Particle Size; D026361:Reactive Nitrogen Species / Q000633:toxicity*; D017382:Reactive Oxygen Species
chemical_list: D000393:Air Pollutants; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase