Involvement of Cytosolic Phospholipase A 2 α in MMP-9 Up-regulation

Abstract

Matrix metalloproteinase-9 (MMP-9) is important in the pathogenesis of periodontitis. Cytosolic phospholipase A₂α (cPLA₂α) is involved in MMP-9 up-regulation in human monocytes. We tested the hypothesis that cPLA₂α 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. cPLA₂α mRNA was constitutively expressed in gingival epithelial cells. Transient activation of cPLA₂ by Ser505 phosphorylation was observed in the nuclei upon stimulation, suggesting its role as a transcription factor, while cPLA₂ protein expression remained unchanged. Induction of MMP-9 expression and activity was significantly inhibited by 1 μM of the specific cPLA₂α inhibitor (P < 0.01). These findings demonstrate the involvement of cPLA₂α in MMP-9 up-regulation.

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