Effects of nifedipine and interleukin-1alpha on the expression of collagen, matrix metalloproteinase-1, and tissue inhibitor of metalloproteinase-1 in human gingival fibroblasts.
OBJECTIVE
Nifedipine-induced gingival overgrowth is known to be characterized by fibrosis and some degree of inflammation. However, the molecular mechanism of the fibrosis is not fully understood. The purpose of this study was to investigate in vitro the effects of nifedipine and interleukin-1alpha on the molecules involved in fibrosis, namely type I collagen, matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1).


METHODS
Four human gingival fibroblast strains, derived from four healthy volunteers, were cultured in media containing nifedipine (1 microg/ml), with or without interleukin-1alpha (0.05 ng/ml). The mRNAs of type I collagen, MMP-1, and TIMP-1 were measured by reverse transcription-polymerase chain reaction (RT-PCR). The proteins of MMP-1 and TIMP-1 were examined by enzyme-linked immunosorbent assay (ELISA), and the ratios of MMP-1 to TIMP-1 proteins were calculated.


RESULTS
The mRNA expression of type I collagen showed no significant change. Both mRNA expression and protein production of MMP-1 were up-regulated by interleukin-1alpha, either alone or in combination with nifedipine, whereas those of TIMP-1 were up-regulated by nifedipine alone or in combination with interleukin-1alpha. The ratio of MMP-1 to TIMP-1 was not changed by nifedipine alone, but it was increased by interleukin-1alpha alone or in combination with nifedipine. However, in two of the four cell strains tested, nifedipine reduced the ratio of MMP-1 to TIMP-1 compared with that for interleukin-1alpha alone.


CONCLUSIONS
These results suggest that nifedipine may predispose to fibrosis in some individuals in situations where interleukin-1 levels are raised.
Sakagami
G
G
Department of Pathology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
Sato
E
E
Sugita
Y
Y
Kosaka
T
T
Kubo
K
K
Maeda
H
H
Kameyama
Y
Y
D000293:Adolescent; D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D009543:Nifedipine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
D002121:Calcium Channel Blockers; D024042:Collagen Type I; D007375:Interleukin-1; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020781:Matrix Metalloproteinase 1; D009543:Nifedipine