Cigarette smoke and reactive oxygen species metabolism: implications for the pathophysiology of Reinke's edema

Abstract

Objective/hypothesis: Oxidative damage mediates the lower airway response to cigarette smoke (CS). In the vocal folds, the tissue phenotype is both distinct and largely uncharacterized. We sought to investigate the effects of CS on the oxidative status and fibroblast phenotype in the vocal folds. Specifically, we hypothesized that CS would induce a hypermetabolic fibroblast phenotype and altered oxidative metabolism potentially providing insight into the relationship among CS, Reinke's edema (RE), and malignancy.

Study design: In vivo/in vitro.

Methods: Heme oxygenase (HO)-1 gene expression was examined in human tissue. In vitro, the effects of cigarette smoke condensate (CSC) on HO-1 gene expression and secretion was assayed. In addition, CS-mediated intracellular reactive oxygen species synthesis was quantified, and compared to the response in pulmonary fibroblasts (HFL). We then examined the effects of CSC on migration and proliferation in human vocal fold fibroblasts (HVOX).

Results: : HO-1 expression was approximately 4-fold higher in RE samples versus vocal fold polyps. CSC induced HO-1 gene expression and secretion in a time- and dose-dependent fashion in vitro. CSC also increased intracellular ROS in both HVOX and HFL. CSC decreased HVOX proliferation and migration in a dose-dependent manner.

Conclusions: These data suggest that the fibroblast phenotype is influenced by smoke. Our data suggest that the antioxidant response in the vocal fold tissue may be one mechanism of chemoprotection, a putative explanation for the observation that RE rarely transforms to malignancy. In addition, CSC does not appear to induce a hypermetabolic fibroblast phenotype as expected.