Abstract
In this study, we examined the reversing effect of thiol anti-oxidant N-acetylcysteine (NAC) on cigarette smoke component-induced MHC class II downregulation, chronic inflammation cytokine gene switch, and cell migration using human bronchial epithelial cells BEAS-2B as a model. Crude cigarette smoke extract (CSE) (3%) induced marked downregulation of MHC class II and of acute inflammation cytokine CXCL12 gene expression. In addition, upregulated chronic inflammation cytokine genes CCL19 and CTGF, as well as neutrophil-stimulating cytokine gene G-CSF were found in BEAS-2B cells. NAC administered at 1 mM in the presence of CSE (3%) rescued MHC class II downregulation and reversed CCL19 upregulation, but had no effect on CXCL12, CTGF, and G-CSF in BEAS-2B cells. Among the four major cigarette compounds nicotine, benzo[a]pyrene, hydrogen peroxide, and acrolein tested, acrolein was able to markedly downregulate MHC class II and CXCL12, which was NAC-reversible, while hydrogen peroxide induced G-CSF, which could be suppressed by NAC by ~50%. These results suggest the existence of some cigarette component specificity underlying differential types of CSE-induced immune dysregulation, which were also differentially rescued by NAC. The failure of NAC to rescue CSE-induced CXCL12 downregulation may be attributable to the presence of multiple pathways leading to repression of this chemokine gene. CSE, acrolein and hydrogen peroxide delay cell migration in BEAS-2B cells, while benzo[a]pyrene enhances cell migration in BEAS-2B cells. Either delay or enhance caused by CSE components could be reversed by NAC. Thus, NAC may have potential to counteract defective MHC class II-associated antigen presentation, to reverse, to some extent, chronic inflammation cytokine gene switch and to correct abnormal cell migration in lung diseases caused by cigarette smoking.