Expression and bioactivities of endothelin-1 in gingiva during cyclosporine A treatment.
OBJECTIVE
This study aimed to evaluate the expression and bioactivities of endothelin-1 (ET-1) in gingiva during cyclosporine A (CsA) treatment.


METHODS
After establishing edentulous ridges, experimental rats were fed 30 mg/kg/day CsA while control animals received mineral oil for 4 weeks, after which a reverse transcription-polymerase chain reaction (RT-PCR) and/or immunohistochemistry was used to examine the expression of ET-1, its receptors, proliferating cell nuclear antigen (PCNA) and inducible nitric oxide synthase (iNOS) in gingivae. The roles of the endothelin receptors A and B (ET(A) and ET(B)) in CsA-enhanced expression of PCNA and iNOS were examined in cultured human gingival fibroblasts pretreated with receptor antagonists, by immunocytochemistry and RT-PCR, respectively.


RESULTS
The mRNA expression of ET-1, ET(A) and ET(B), as well as of PCNA and iNOS, was significantly greater in edentulous gingiva that received CsA compared with control gingiva. Immunohistochemistry revealed more cells positively stained for ET-1 and its receptors in the tissues of CsA-treated rats than in those of control rats. In fibroblast cultures, enhanced mRNA expression of ET-1, ET(A) and ET(B) was observed after CsA treatment at the concentrations of 10 and 100 ng/mL. Cyclosporine A-enhanced PCNA expression was somewhat reduced by blockade of ET(A), but not ET(B), whereas iNOS expression was somewhat reduced by blockade of ET(B).


CONCLUSIONS
Based on the present findings, we suggest that: (1) CsA upregulates the gingival expression of ET-1 and its receptors; and (2) ET(A) and ET(B) have different bioactivities, ET(A) being involved in cell proliferation and ET(B) being associated with iNOS expression.
Chin
Y-T
YT
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Tu
H-P
HP
Chen
Y-T
YT
Dai
N-T
NT
Shen
E-C
EC
Chiang
C-Y
CY
Fu
M M-J
MM
Fu
E
E
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000032:analysis* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005881:Gingiva / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D009066:Mouth, Edentulous / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D044022:Receptor, Endothelin A / Q000032:analysis; D044023:Receptor, Endothelin B / Q000032:analysis; D015854:Up-Regulation
D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D007166:Immunosuppressive Agents; D018809:Proliferating Cell Nuclear Antigen; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D016572:Cyclosporine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat