TITLE:
Role of Rac1/p38 and ERK-Dependent Cytosolic Phospholipase A2 Activation in Porphyromonas gingivalis-Evoked Induction in Matrix Metalloproteinase-9 (MMP-9) Release by Salivary Gland Cells
AUTHORS:
Bronislaw L. Slomiany, Amalia Slomiany
KEYWORDS:
P. gingivalis LPS, Oral Mucosa, Rac1, p38, ERK, cPLA2 Activation MMP-9 Release
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.4 No.4,
April
26,
2016
ABSTRACT: Matrix
metalloproteinase-9 (MMP-9) is a highly glycosylated endopeptidase implicated
in a wide rage of oral mucosal inflammatory and neoplastic diseases, including
chronic periodontitis, a persistent mucosal inflammation attributed primarily
to infection by oral anaerobe, P.
gingivalis. In this study, we explored the role of Rac1 and
mitogen-activated protein kinases (MAPKs) in the processes of MMP-9 release in
sublingual salivary gland cells exposed to P.
gingivalis key endotoxin, cell wall lipopolysaccharide (LPS). We
demonstrate that the LPS-elicited induction in the acinar cell MMP-9 release is
associated with MAPK, ERK and p38 activation, and occurs with the involvement
of Rac1 and cytosolic phospholipase A2 (cPLA2). Further,
we reveal that the LPS-induced MMP-9 release involves ERK-mediated phosphorylation
of cPLA2 on Ser505 that is essential for its membrane
translocation with Rac1, and that this process requires p38 activation.
Moreover, we show that phosphorylation and membrane localization of p38 with
Rac1-GTP play a pivotal role in cPLA2-dependent induction in MMP-9
release. Thus collectively, our findings infer that P. gingivalis LPS-induced up-regulation in the acinar cell MMP-9
release requires ERK-dependent recruitment of cPLA2 to the membrane
localized Rac1/p38 complex.