Upregulation of heme oxygenase-1 expression in gingiva after cyclosporin A treatment

J Periodontol. 2008 Nov;79(11):2200-6. doi: 10.1902/jop.2008.080160.

Abstract

Background: Heme oxygenase (HO)-1 is a stress-inducible protein that confers cytoprotection, but its role in gingiva during cyclosporin A (CsA) therapy is unknown. We used in vivo and in vitro models to investigate the expression of mRNA and protein for HO-1 in gingiva upon CsA treatment.

Methods: Twenty-six male Sprague-Dawley rats were assigned to two groups after the establishment of edentulous ridges. Rats in the CsA group received CsA, 30 mg/kg/day for 4 weeks, whereas control rats received mineral oil only. All rats were killed after 4 weeks, and the edentulous gingivae were excised. mRNA and protein expression of HO-1 in gingivae were determined using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), respectively. For the in vitro study, cultured human gingival fibroblasts were harvested after treatment with various concentrations of CsA, and HO-1 mRNA and protein expression were determined using RT-PCR and Western blotting, respectively.

Results: Mean gingival HO-1 mRNA expression was greater in the CsA group than in the control animals (P = 0.076). IHC staining for HO-1 protein was significantly greater in the gingivae of CsA-treated rats than in those of the control group. In fibroblast cultures, expression of HO-1 mRNA and protein also increased significantly after CsA treatment.

Conclusion: CsA upregulates the gingival expression of HO-1, which may exert a cytoprotective effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cyclosporine / adverse effects
  • Cyclosporine / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Gingiva / cytology
  • Gingiva / drug effects
  • Gingiva / enzymology*
  • Gingival Hyperplasia / chemically induced
  • Gingival Hyperplasia / enzymology*
  • Gingival Hyperplasia / prevention & control
  • Heme Oxygenase-1 / drug effects
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacology*
  • Male
  • RNA, Messenger / analysis
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation

Substances

  • Immunosuppressive Agents
  • RNA, Messenger
  • Cyclosporine
  • Heme Oxygenase-1