Role of Rac1/p38 and ERK-Dependent Cytosolic Phospholipase A<sub>2</sub> Activation in <i>Porphyromonas gingivalis</i>-Evoked Induction in Matrix Metalloproteinase-9 (MMP-9) Release by Salivary Gland Cells

Abstract

How to cite this paper: Slomiany, B.L. and Slomiany, A. (2016) Role of Rac1/p38 and ERK-Dependent Cytosolic Phospholipase A 2 Activation in Porphyromonas gingivalis-Evoked Induction in Matrix Metalloproteinase-9 (MMP-9) Release by Salivary Gland Cells.

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

“…Moreover, these responses to P. gingivalis are mediated through the LPS triggered TLR4 activation [18] [33].…”

“…Therefore, taking into account the evidence that MMP-9 undergoes extensive processing in the Golgi network and the fact that oral mucosal inflammatory responses to P. gingivalis are characterized by the rapid rise in MMP-9 release, we investigated the nature of factors involved in the processing of signaling cascade initiated by the LPS [18]. As summarized in Figure 2, our findings demonstrated that P. gingivalis LPS-elicited induction in the salivary gland acinar cell MMP-9 release is associated with MAPK, ERK and p38 activation, and occurs with the involvement of Rac1 and cPLA 2 ).…”

“…Indeed, P. gingivalis, by far the most prominent member of the bacterial flora found in periodontal packets of people with gum disease [12], has to its disposal an impressive array of virulence factors that provoke the inflammatory response of the host tissue [13] [14]. These include its cell surface major (FimA) and minor (Mfa1) fimbriae proteins, elaborated arginine and lysine specific cysteine proteinases, referred to as gingipain R and gingipain K [15] [16], collagenases, capable of extracellular matrix proteins degradation and activation of the host matrix metalloproteinases [17] [18] [19], and the secreted sufatases directed towards cell membrane glycosphingolipids as well as proteoglycans of extracellular matrix [3] [20]. However, the virulence factor of particular significance to the pathogenic action of P. gingivalis leading to the development of periodontitis is its cell-wall lipopolysaccharide (LPS) [21] [22].…”

“…The endotoxin and the immunological properties of LPS reside mainly in the heterogeneous acylation character of lipid A domain, which in different bacterial species shows considerable variation in the acylation pattern and the number of phosphate groups, while the core and O-specific regions of LPS appear to have only minor role in the immune recognition [23] [24] [26] [27] [28]. Journal of Biosciences and Medicines Investigations into the events associated with oral mucosal responses to P. gingivalis LPS demonstrated a marked increase in epithelial cell apoptosis and proinflammatory cytokine expression, up-regulation in endothelin-1 (ET-1) and TNF-α release, excessive nitric oxide (NO) and prostaglandin (PGE2) generation, and the elevated levels of matrix metalloproteinase-9 (MMP-9) production [18] [33]. Hence, considering that the elevated levels of MMP-9, along with the increased proinflammatory cytokine production are implicated in pathogenesis of chronic periodontitis, in this article we review data on the signaling pathways engaged by periodontopathogen, P. gingivalis, in controlling the processing and secretion of MMP-9.…”

Role of Signal-Regulated Changes in Microtubule Stability Dynamics through <i>α</i>-Tubulin Phosphorylation on Ser/Tyr in Modulation of Salivary Gland Matrix Metalloproteinase-9 (MMP-9) Secretion in Response to <i>Porphyromonas gingivalis</i> and Ghrelin

“…The oral mucosal responses to P. gingivalis and its key endotoxin, cell-wall lipopolysaccharide (LPS), are characterized by the disturbances in nitric oxide synthase and cyclooxygenase systems, up-regulation in EGFR and MAPK activation, and induction in the secretion of highly glycosylated endopeptidase, metalloproteinase-9 (MMP-9) [4] [5] [6] [7] [8]. Similarly, to other regulated secretory proteins, the processing of MMP-9 along the endoplasmic reticulum (ER), Golgi, and trans-Golgi network (TGN) remains under a strict control of factors that affect the membrane recruitment and activation of various coat and cargo proteins, including ADPribosylation factors (Arfs) and protein kinase D (PKD), [9] [10] [11] [12].…”