Involvement of cytosolic phospholipase A2alpha in MMP-9 up-regulation
P Montreekachon1, P Chotjumlong, V Reutrakul
1Center of Excellence for Innovation in Chemistry, Department of Odontology and Oral Pathology, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand.
Abstract:
Matrix metalloproteinase-9 (MMP-9) is important in the pathogenesis of periodontitis. Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) is involved in MMP-9 up-regulation in human monocytes. We tested the hypothesis that cPLA(2)alpha also regulates MMP-9 induction by Fusobacterium nucleatum and by phorbol 12-myristate-13-acetate (PMA) in gingival epithelial cells. While PMA induced MMP-9 expression considerably, F. nucleatum did so moderately. This time-course study demonstrated that MMP-9 mRNA up-regulation occurred at 3 hours, whereas MMP-9 secretion and activity in cell-free supernatants occurred at 12 hours. cPLA(2)alpha mRNA was constitutively expressed in gingival epithelial cells. Transient activation of cPLA(2) by Ser505 phosphorylation was observed in the nuclei upon stimulation, suggesting its role as a transcription factor, while cPLA(2) protein expression remained unchanged. Induction of MMP-9 expression and activity was significantly inhibited by 1 muM of the specific cPLA(2)alpha inhibitor (P < 0.01). These findings demonstrate the involvement of cPLA(2)alpha in MMP-9 up-regulation.
Insights
Cytosolic phospholipase A2alpha (cPLA2alpha) regulates matrix metalloproteinase-9 (MMP-9) in gingival cells. Inhibition of cPLA2alpha significantly reduced MMP-9 induction by Fusobacterium nucleatum and PMA, highlighting its role in periodontitis pathogenesis.
Area of Science:
- Oral Biology
- Molecular Biology
- Enzymology
Background:
- Matrix metalloproteinase-9 (MMP-9) plays a key role in periodontitis pathogenesis.
- Cytosolic phospholipase A2alpha (cPLA2alpha) is known to up-regulate MMP-9 in human monocytes.
Purpose of the Study:
- To investigate the role of cPLA2alpha in MMP-9 induction by Fusobacterium nucleatum and phorbol 12-myristate-13-acetate (PMA) in gingival epithelial cells.
Main Methods:
- Time-course study of MMP-9 mRNA and protein expression and activity.
- Assessment of cPLA2alpha activation via phosphorylation.
- Inhibition of cPLA2alpha using a specific inhibitor.
Main Results:
- PMA and F. nucleatum induced MMP-9 expression and activity in gingival epithelial cells.
- MMP-9 mRNA levels increased at 3 hours, while secretion and activity peaked at 12 hours.
- cPLA2alpha activation, indicated by Ser505 phosphorylation in the nucleus, correlated with MMP-9 induction.
- A specific cPLA2alpha inhibitor significantly reduced MMP-9 induction (P < 0.01).
Conclusions:
- cPLA2alpha is involved in the up-regulation of MMP-9 in gingival epithelial cells.
- These findings suggest cPLA2alpha as a potential therapeutic target in periodontitis.
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