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


CONCLUSIONS
CsA upregulates the gingival expression of HO-1, which may exert a cytoprotective effect.
Chiu
Hsien-Chung
HC
National Defense Medical Center, Taipei, Taiwan.
Lan
Guo-Lun
GL
Chiang
Cheng-Yang
CY
Chin
Yu-Tang
YT
Tu
Hsiao-Pei
HP
Ming-Jen Fu
Martin
M
Shin
Nieh
N
Fu
Earl
E
D000818:Animals; D002478:Cells, Cultured; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005885:Gingival Hyperplasia / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine; D051547:Heme Oxygenase-1