Crotonaldehyde-exposed macrophages induce IL-8 release from airway epithelial cells through NF-κB and AP-1 pathways

Crotonaldehyde, a highly toxic α, β-unsaturated aldehyde, is a major component of cigarette smoke and a ubiquitous environmental pollutant. Crotonaldehyde exposure is known to have adverse effects on respiratory health, but the underlying mechanisms remain obscure. To examine the interaction between macrophages and airway epithelial cells after exposure to crotonaldehyde, BEAS-2B and A549 cells were treated with conditioned media from a human monocytic leukemia cell line (THP-1) cells stimulated with crotonaldehyde. We demonstrate that conditioned media from THP-1 cells stimulated with crotonaldehyde increased interleukin (IL)-8 production, enhanced nuclear factor (NF)-κB and AP-1 DNA-binding activity in BEAS-2B and A549 cells. Analysis of these conditioned media revealed marked increases in tumor necrosis factor (TNF)-α, IL-1β and IL-8 levels. Preincubation of conditioned media with either TNF-α- or IL-1β-neutralizing antibodies reduced IL-8 production. Furthermore, BEAS-2B and A549 cells directly treated with crotonaldehyde induced increase in IL-8 production. These data suggest that crotonaldehyde is capable of directly stimulating the production of IL-8 in both macrophages and airway epithelial cells. Crotonaldehyde-stimulated macrophages also amplify the inflammatory response by enhancing IL-8 release from airway epithelial cells mediated by NF-κB and AP-1 pathways through a mechanism involving TNF-α and IL-1β. These findings indicate that crotonaldehyde can cause lung inflammatory response via multiple mechanisms, and may contribute to chronic airway inflammation in smokers.

Figure optionsDownload as PowerPoint slideHighlights
► Crotonaldehyde induced increase in IL-8, TNF-α and IL-1β production in THP-1.
► Crotonaldehyde-exposed macrophages induce IL-8 release from BEAS-2B and A549.
► Crotonaldehyde-exposed macrophages enhanced NF-κB, AP-1 activity in BEAS-2B, A549.
► TNF-α-, IL-1β-neutralizing antibodies reduced IL-8 production in BEAS-2B and A549.
► Crotonaldehyde induced increase in IL-8 production in BEAS-2B and A549.