Heme oxygenase-1 mediates nicotine- and lipopolysaccharide-induced expression of cyclooxygenase-2 and inducible nitric oxide synthase in human periodontal ligament cells

Background and Objective: Although heme oxygenase-1 (HO-1) plays a key role in inflammation, its anti-inflammatory effects and mechanism of action in periodontitis are still unknown. This study aimed to identify the effects of HO-1 on the proinflammatory mediators activated by nicotine and lipopolysaccharide (LPS) stimulation in human periodontal ligament (PDL) cells. Material and Methods: The production of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) was evaluated using Griess reagent and an enzyme immunoassay, respectively. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and HO-1 proteins was evaluated by Western blot analysis. Results: Lipopolysaccharide and nicotine synergistically induced the production of NO and PGE(2) and increased the protein expression of iNOS, COX-2 and HO-1. Treatment with an HO-1 inhibitor and HO-1 small interfering RNAs blocked the LPS- and nicotine-stimulated NO and PGE(2) release as well as the expression of iNOS and COX-2. Conclusion: Our data suggest that the nicotine- and LPS-induced inflammatory effects on PDL cells may act through a novel mechanism involving the action of HO-1. Thus, HO-1 may provide a potential therapeutic target for the treatment of periodontal disease associated with smoking and dental plaque.