Upregulation of the Protective Heme Oxygenase Enzyme in Periodontitis

Heme oxygenase (HO) catalyzes the rate limiting step in the oxidation of heme to biliverdin, free iron, and carbon monoxide. Two forms of HO have been identified: inducible HO-1 (also termed as HSP-32) and constitutive HO-2. Recent studies demonstrated that the expression of HO-1 have protective effects on injuries including gastrointestinal inflammations. These beneficial effects seem to be due to the removal of free heme, which is toxic for the host and a usable source of bacterial proliferation, furthermore, to the production of bile pigments, which are potent antioxidants. Objectives: Here we studied the HO isoforms in the gingivomucosal tissue using a rat model of periodontitis. Methods: Periodontitis was produced by a silk ligature placed around the cervix of the lower left 1st molar. At Day 8, the gingivomucosal tissues encircling the mandibular 1st molars were harvested on both sides and their HO activity were determined by bilirubin formation test or were immunostained with anti-HO-1/anti-HO-2 antibodies using ABC protocol. Results: Periodontitis significantly elevated tissue HO activity compared to the contralateral control side (46±11 vs. 18±5 nmol/mg/h). Immunohistochemical analysis revealed a significantly increased HO-1 staining in the vessel wall, fibroblasts, fibrocytes, mast cells and in the inflammatory infiltrating cells in the subepithelial connective tissue, and also in the middle layer of the epithelium of the ligated side compared to the contralateral side. On the other hand, HO-2 immunolabelling, which was expressed in nerve fibers in the healthy gingiva, remained virtually unaltered in the periodontitis affected gingiva. Conclusions: Our observations suggest that both HO-1 and HO-2 izoenzymes are found in resting condition in the gingiva. HO-1 expression is significantly increased in periodontitis. We propose that the activation of HO may act as a natural defensive mechanism to ameliorate tissue injury. Support: Hungarian OTKA T042584 and T049708. Email: Lohinai@elet2.sote.hu