Document Detail

Cyclosporine A inhibits the expression of membrane type-I matrix metalloproteinase in gingiva.
MedLine Citation:
PMID:  19210333     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND OBJECTIVE: Membrane type-I matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase-2 (TIMP-2) regulate the activation of MMP-2; however, their roles in the activation of MMP-2 in gingiva during treatment with cyclosporine A are still unknown. Therefore, the expressions of membrane type-I MMP and TIMP-2, as well as MMP-2, in gingivae upon treatment with cyclosporine A were examined in vivo and in vitro. MATERIAL AND METHODS: Thirty-four rats were divided into two groups after edentulous ridges were established. The experimental group received 30 mg/kg/d of cyclosporine A and the control group received vehicle. At the end of the experimental period, the rats were killed, the gingivae were obtained and the expression of mRNA and protein of membrane type-I MMP, TIMP-2 and MMP-2 in gingiva were examined using real-time polymerase chain reaction and immunohistochemistry. In human gingival fibroblasts, the activity of MMP-2 and the expression of MMP-2, membrane type-I MMP and TIMP-2 mRNAs were examined (using zymography and reverse transcription-polymerase chain reaction, respectively) after treatment with cyclosporine A. RESULTS: In gingivae of rats, cyclosporine A significantly decreased the expression of mRNA and protein of membrane type-I MMP, but not of TIMP-2. The expression of MMP-2 mRNA was unaffected but the expression of MMP-2 protein showed a significant decrease upon treatment with cyclosporine A. In fibroblast culture medium, the presence of cyclosporine A induced a decrease in MMP-2 activity in a dose-dependent manner. The expression of MMP-2, membrane type-I MMP and TIMP-2 mRNAs in fibroblasts was not significantly affected by cyclosporine A; however, in fibroblasts the ratio of mRNA expression of membrane type-I MMP to that of TIMP-2 decreased as the cyclosporine A dose was increased. CONCLUSION: Cyclosporine A inhibits the expression of membrane type-I MMP in gingiva and it may further reduce the activation of MMP-2.
H-C Chiu; Y-T Lu; Y-T Chin; H-P Tu; C-Y Chiang; C-H Gau; S Nieh; E Fu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-06
Journal Detail:
Title:  Journal of periodontal research     Volume:  44     ISSN:  1600-0765     ISO Abbreviation:  J. Periodont. Res.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-20     Completed Date:  2009-08-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0055107     Medline TA:  J Periodontal Res     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  338-47     Citation Subset:  D; IM    
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, China.
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MeSH Terms
Cell Survival / drug effects
Cells, Cultured
Cyclosporine / pharmacology*
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Fibroblasts / drug effects,  enzymology
Gene Expression / drug effects
Gingiva / cytology,  drug effects,  enzymology*
Gingival Overgrowth / chemically induced,  enzymology
Immunosuppressive Agents / pharmacology*
Matrix Metalloproteinase 1 / biosynthesis
Matrix Metalloproteinase 14 / antagonists & inhibitors*,  biosynthesis
Matrix Metalloproteinase 2 / antagonists & inhibitors*,  biosynthesis
Protease Inhibitors / pharmacology*
RNA, Messenger / biosynthesis
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinase-2 / biosynthesis
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Protease Inhibitors; 0/RNA, Messenger; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; 59865-13-3/Cyclosporine; EC Metalloproteinase 2; EC Metalloproteinase 1; EC Metalloproteinase 14

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