TITLE:
Proinflammatory Pathways Engaged by Oral Pathogen Porphyromonas gingivalis in Upregulation of Matrix Metalloproteinase-9 Expression in Periodontal Disease
AUTHORS:
Bronislaw L. Slomiany, Amalia Slomiany
KEYWORDS:
P. gingivalis, Periodontal Disease, Inflammatory Response, LPS, TLR4, MMP-9
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.6 No.6,
June
25,
2018
ABSTRACT: Matrix
metalloproteinase-9 (MMP-9) is a potent endopeptidase implicated in a wide
range of inflammatory and neoplastic diseases, including chronic periodontitis,
a persistent oral mucosal inflammation attributed primarily to infection by P. gingivalis. Here, we review the
signaling pathways engaged by P.
gingivalis in controlling the processing and secretion of MMP-9. The
induction in oral mucosal expression of MMP-9 by P. gingivalis relays primarily on its key endotoxin, LPS,
engagement of TLR4 and the activation of MAPK, ERK and p38 cascades implicated
in the stimulation of Rac1 and cPLA2. The ERK-mediated cPLA2 phosphorylation plays an essential role in its membrane translocation with
Rac1, while p38 localization with Rac1 promotes cPLA2 activation and
the induction in MMP-9. Moreover, the induction in MMP-9 secretion by the LPS
and the modulatory influence of peptide hormone, ghrelin, occur at the level of
MMP-9 processing between ER and Golgi, with the involvement of factors that
control secretory cargo sorting, Arf1 GTPase and PKD2. The secretion of MMP-9,
furthermore, occurs in concert with the changes in stability dynamics of
microtubules (MTs), which affect the Golgi localization of Arf1 and the
recruitment and activation of PKD2. The induction in MMP-9 secretion by LPS is
accompanied by the enhancement in MT stabilization and α-tubulin phosphorylation on Ser, while the MT
destabilization associated with the modulatory influence of ghrelin, is
manifested by α-tubulin phosphorylation on Tyr. Thus, the factors
capable of affecting MT dynamics and MMP-9 secretion present a tempting target
for the therapeutic intervention in the treatment of chronic periodontitis.