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Involvement of Cytosolic Phospholipase A2 in MMP-9 Up-regulation
P. Montreekachon1,
P. Chotjumlong1,
V. Reutrakul2 and
S. Krisanaprakornkit1,*
1 Center of Excellence for Innovation in Chemistry, Department of Odontology and Oral Pathology, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand; and
2 Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Correspondence: * sutichai{at}chiangmai.ac.th or suttichaikris{at}yahoo.com
Matrix metalloproteinase-9 (MMP-9) is important in the pathogenesis of periodontitis. Cytosolic phospholipase A2 (cPLA2 ) is involved in MMP-9 up-regulation in human monocytes. We tested the hypothesis that cPLA2 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. cPLA2 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 cPLA2 inhibitor (P < 0.01). These findings demonstrate the involvement of cPLA2 in MMP-9 up-regulation.
Key Words: cPLA2 MMP-9 Fusobacterium nucleatum gene regulation gingival epithelial cells
Journal of Dental Research, Vol. 88, No. 11,
1031-1036 (2009)
DOI: 10.1177/0022034509345967

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