Matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 production in human gingival fibroblasts: the role of protein kinase C.
J Periodontal Res
; 39(5): 308-14, 2004 Oct.
Article
em En
| MEDLINE
| ID: mdl-15324351
ABSTRACT
BACKGROUND:
Matrix metalloproteinase-1 (MMP-1) plays an important role in tissue remodelling and in the pathology of inflammatory diseases including periodontitis. The activity of MMP-1 is firmly controlled by the endogenous tissue inhibitor of metalloproteinase-1 (TIMP-1).OBJECTIVE:
The aim of the study was to investigate the production and regulation of MMP-1 and TIMP-1 with special regards to the enzyme protein kinase C (PKC) in human gingival fibroblasts.METHODS:
Gingival fibroblasts were treated with substances related to PKC such as phorbol 12-myristate 13-acetate (PMA), interleukin-1beta, Ca2+ -ionophore A231817 and inhibitors of PKC, p38 mitogen-activated protein kinase (p38 MAPK) and tyrosine kinase.RESULTS:
The PKC activator PMA stimulated the production of MMP-1 and TIMP-1 at both the transcriptional and the translational level. The production of MMP-1 and TIMP-1 stimulated by PMA was abolished by the PKC inhibitor bisindolylmaleimide. Treatment of the cells with interleukin-1beta or A23187 synergistically increased the stimulatory effect of PMA on MMP-1 production. In contrast, TIMP-1 production was unaffected by interleukin-1beta and reduced by A23187. Tyrosine kinase inhibitor herbimycin A reduced MMP-1 production induced by PMA, whereas the p38 MAPK-inhibitor SB 203580 synergistically increased the stimulatory effect of PMA on both MMP-1 and TIMP-1 production.CONCLUSION:
The present study shows that MMP-1 and TIMP-1 production is regulated differently by interleukin-1beta and calcium in human gingival fibroblasts and that this difference is markedly amplified in the presence of the PKC-activator PMA. Taken together, the discrepancy in the production of MMP-1 and TIMP-1 in gingival fibroblasts may contribute to tissue destruction in periodontal diseases.
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Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
/
Inibidor Tecidual de Metaloproteinase-1
/
Metaloproteinase 1 da Matriz
/
Gengiva
Limite:
Adolescent
/
Child
/
Child, preschool
/
Humans
/
Infant
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article