Inhibition of NFκB activation and IL-8 expression in human bronchial epithelial cells by acrolein

Giuseppe Valacchi, Elisa Pagnin, Anh Phung, Mirella Nardini, Bettina C. Schock, Carroll E Cross, Albert Van Der Vliet

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Lipid oxidation and environmental pollutants are major sources of α,β-unsaturated aldehydes such as acrolein and 4-hydroxynonenal. Acrolein (2-propenal), a major product of organic combustion such as tobacco smoke, represents the most reactive α,β-unsaturated aldehyde, with high reactivity toward nucleophilic targets such as sulfhydryl groups. To investigate how acrolein affects respiratory tract cell activation, we exposed either primary (NHBE) or immortalized human bronchial epithelial cells (HBE1) to 0-25 μM acrolein, and determined effects on basal and tumor necrosis factor-α (TNFα)-induced production of the chemokine interleukin (IL)-8. Cell exposure to acrolein dose-dependently suppressed IL-8 mRNA levels in HBE1 cells (26, 40, and 79% at 5, 10, and 25 μM acrolein concentrations, respectively) and resulted in corresponding decreases in IL-8 production. Studies of nuclear factor-κB (NFκB) activation, an essential event in IL-8 production, showed decreased TNFα-induced NFκB activation by acrolein, illustrated by inhibition of nuclear translocation of NFκB and reduced IκBα degradation. Immunochemical analysis of IκB kinase (IKK), a redox-sensitive regulator of NFκB activation, indicated direct modification of the IKK β-subunit by acrolein, suggesting that acrolein may act directly on IKK. In summary, our results demonstrate that acrolein can suppress inflammatory processes in the airways by inhibiting epithelial IL-8 production through direct or indirect inhibitory effects on NFκB activation.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalAntioxidants and Redox Signaling
Volume7
Issue number1-2
DOIs
StatePublished - Jan 2005

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Inhibition of NFκB activation and IL-8 expression in human bronchial epithelial cells by acrolein'. Together they form a unique fingerprint.

  • Cite this