Augmented heme oxygenase-1 expression in areca quid chewing-associated oral submucous fibrosis

Heme oxygenase-1 (HO-1) is known as a stress-inducible protein and functions as an antioxidant enzyme. HO-1 is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare HO-1 expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induce HO-1 expression. Twenty OSF specimens and 10 normal buccal mucosa were examined by immunohistochemistry. The mRNA levels of HO-1 from fibroblasts cultured from OSF and normal buccal mucosa fibroblasts (BMFs) were evaluated by reverse transcription polymerase chain reaction. The effect of arecoline, the major areca nut alkaloid, was added to explore the potential mechanism that may lead to induce HO-1 expression. Heme oxygenase-1 expression was significantly higher in OSF specimens (P < 0.05) and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. OSF demonstrated significantly higher HO-1 mRNA expression than BMFs (P < 0.05). Arecoline was also found to elevate HO-1 mRNA and protein expression in a dose-dependent manner (P < 0.05). Taken together, the data presented here demonstrated that HO-1 expression is significantly upregulated in OSF from areca quid chewers, and arecoline may be responsible for the enhanced HO-1 expression in vivo.