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


METHODS
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.
Branski
Ryan C
RC
Department of Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, 1275 YorkAvenue, New York, NY 10065, USA. branskir@mskcc.org
Saltman
Benjamin
B
Sulica
Lucian
L
Szeto
Hazel
H
Duflo
Suzy
S
Felsen
Diane
D
Kraus
Dennis H
DH
D002465:Cell Movement; D049109:Cell Proliferation; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007819:Laryngeal Edema / Q000473:pathology / Q000503:physiopathology*; D007820:Laryngeal Mucosa / Q000473:pathology; D008168:Lung / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000378:metabolism* / Q000503:physiopathology
D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1