Polycyclic aromatic hydrocarbons induce IL-8 expression through nuclear factor kappaB activation in A549 cell line

Cytokine. 2002 Sep 7;19(5):236-41.

Abstract

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.

MeSH terms

  • Cell Line
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation / drug effects*
  • Humans
  • I-kappa B Proteins / metabolism
  • Interleukin-8 / genetics*
  • Interleukin-8 / metabolism*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Polycyclic Aromatic Hydrocarbons / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription, Genetic / drug effects

Substances

  • I-kappa B Proteins
  • Interleukin-8
  • NF-kappa B
  • NFKBIA protein, human
  • Polycyclic Aromatic Hydrocarbons
  • RNA, Messenger
  • NF-KappaB Inhibitor alpha