Polycyclic aromatic hydrocarbons induce IL-8 expression through nuclear factor kappaB activation in A549 cell line.
Air pollution causes increased cardiopulmonary morbidity and mortality. Airway inflammation plays a major role in the pathophysiology of many lung diseases. Proinflammatory cytokines, such as interleukin-8 (IL-8), are responsible in part for the initiation and maintenance of airway inflammation. Asbestos exposure and particulate air pollution have been reported to stimulate the expression of IL-8 and to induce NF-kappaB activation. However, it is unknown whether polycyclic aromatic hydrocarbons (PAH), mainly existed in most airborne particulates, can separately induce IL-8 expression. In the present study, we investigated the effect of benzo(a)pyrene (B[a]P) and 1-nitropyrene (1-NP), two representative PAH, on IL-8 expression using ELISA and Northern blot analysis. Gel shift assay was performed to study the NF-kappaB activation. We have assessed the effect of adenovirus-mediated overexpression of the NF-kappaB inhibitor, IkappaBalpha on PAH-induced IL-8 expression in A549 cell line. Both B[a]P and 1-NP stimulated IL-8 gene expression in A549 cells. This effect was associated with induction of NF-kappaB activation. Overexpression of IkappaBalpha inhibited 1-NP-induced transcription of IL-8. This suggests that PAH-induced IL-8 gene regulation may be mediated by NF-kappaB. These data indicate that PAH alone, either B[a]P or 1-NP, is sufficient to stimulate NF-kappaB activation and IL-8 transcription.
Pei
Xin-Hai
XH
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, Japan.
Nakanishi
Yoichi
Y
Inoue
Hiromasa
H
Takayama
Koichi
K
Bai
Feng
F
Hara
Nobuyuki
N
D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha