%0 Journal Article
%T Proinflammatory Pathways Engaged by Oral Pathogen <i>Porphyromonas gingivalis</i> in Upregulation of Matrix Metalloproteinase-9 Expression in Periodontal Disease
%A Bronislaw L. Slomiany
%A Amalia Slomiany
%J Journal of Biosciences and Medicines
%P 77-94
%@ 2327-509X
%D 2018
%I Scientific Research Publishing
%R 10.4236/jbm.2018.66006
%X 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 <i>P. gingivalis.</i> Here, we review the
signaling pathways engaged by <i>P.
gingivalis </i>in controlling the processing and secretion of MMP-9. The
induction in oral mucosal expression of MMP-9 by <i>P. gingivalis </i>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 cPLA<sub>2</sub>. The ERK-mediated cPLA<sub>2</sub> phosphorylation plays an essential role in its membrane translocation with
Rac1, while p38 localization with Rac1 promotes cPLA<sub>2</sub> 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 <i>¦Á</i>-tubulin phosphorylation on Ser, while the MT
destabilization associated with the modulatory influence of ghrelin, is
manifested by <i>¦Á</i>-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.
%K &lt
%K i&gt
%K P. gingivalis&lt
%K /i&gt
%K Periodontal Disease
%K Inflammatory Response
%K LPS
%K TLR4
%K MMP-9
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=85473