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

Pi S‐H, Jeong G‐S, Oh H‐W, Kim Y‐S, Pae H‐O, Chung H‐T, Lee S‐K, Kim E‐C. Heme oxygenase‐1 mediates nicotine‐ and lipopolysaccharide‐induced expression of cyclooxygenase‐2 and inducible nitric oxide synthase in human periodontal ligament cells. J Periodont Res 2010; 45: 177–183. © 2010 John Wiley & Sons A/S 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 E2 (PGE2) 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 PGE2 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 PGE2 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.