Proinflammatory Pathways Engaged by Oral Pathogen <i>Porphyromonas gingivalis</i>in Upregulation of Matrix Metalloproteinase-9 Expression in Periodontal Disease

• 作者: Amalia Slomiany Bronislaw L. Slomiany
• 来源期刊: 生物科学与医学(英文)
• 学科: 医学
• 关键词: P. gingivalis PERIODONTAL Disease INFLAMMATORY Response LPS TLR4 MMP-9
• 年，卷（期）: 2018,（6）
• 页码范围: 77-94
• 页数: 18页
• 分类号: R73

摘要

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.