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.