title: Crotonaldehyde-exposed macrophages induce IL-8 release from airway epithelial cells through NF-κB and AP-1 pathways.
abstract: 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.
authors: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, Liaoning 116023, PR China.
authors: Bi-Cheng
authors: BC
authors: Yang
authors: Zhi-Hua
authors: ZH
authors: Yang
authors: Xiu-Jie
authors: XJ
authors: Pan
authors: Feng-Jun
authors: FJ
authors: Xiao
authors: Xing-Yu
authors: XY
authors: Liu
authors: Mao-Xiang
authors: MX
authors: Zhu
authors: Jian-Ping
authors: JP
authors: Xie
mesh_terms: D000447:Aldehydes / Q000633:toxicity*; D018929:Cell Culture Techniques; D002460:Cell Line; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D016328:NF-kappa B; D014028:Tobacco Smoke Pollution; D018808:Transcription Factor AP-1; C012796:2-butenal