The role of nitric oxide in the particulate matter (PM2.5)-induced NFkappaB activation in lung epithelial cells.
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.
Nam
Hae Yun
HY
Department of Occupational and Environmental Medicine, St. Mary's Hospital, The Catholic University of Korea, Seoul 150-713, South Korea.
Choi
Byung Hyune
BH
Lee
Joo Yong
JY
Lee
Seok Geon
SG
Kim
Young Hoon
YH
Lee
Kweon Haeng
KH
Yoon
Hyoung Kyu
HK
Song
Jeong Sup
JS
Kim
Hyung Jung
HJ
Lim
Young
Y
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
D000393:Air Pollutants; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase