Proinflammatory Signaling Cascades of Periodontopathic Oral Pathogen <i>Porphyromonas gingivalis</i>

Abstract

Porphyromonas gingivalis, is the most prominent member of the bacteria flora associated with pathogenesis of periodontitis, a chronic inflammatory disease resulting in tooth loss. The extent of oral mucosal reaction to P. gingivalis invasion relays heavily on Toll-like receptors (TLRs) that recognize structurally common motifs of pathogens and initiate antibacterial responses. Among the virulence factors of P. gingivalis implicated in TLRs activation and triggering inflammatory responses leading to the development of periodontitis is the bacterium cell-wall lipopolysaccharide (LPS). The engagement by the LPS of oral mucosal TLR4 leads to initiation of signaling events characterized by the activation of mitogen-activated protein kinase (MAPK) and IκB-kinase complex (IKK) cascades, induction of phosphoinositide-specific phospholipase C (PLC)/protein kinase C (PKC)/PI3K pathway, up-regulation in TGF-α ectodomain shedding and EGFR transactivation, and the amplification of proinflammatory signals by spleen tyrosine kinase (Syk). These events, in turn, exert their control over transcription factors implicated in the induction of the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes that lead to up-regulation in the inflammatory mediators, PGE2 and NO. The systems involved in transcription factors activation, furthermore, remain under additional regulatory control through S-nitrosylation. Moreover, the LPS-induced TLR4 activation provides a docking site for Syk, the activation of which leads to amplification of the inflammatory signals by affecting transcription factors activation and their assembly to transcriptional complexes. Interestingly, the extent of oral mucosal inflammatory response to P. gingivalis remains under modulatory influence by two biologically active peptide hormones, leptin and ghrelin. Therefore, the presence of these multifunctional peptides in oral mucosa and saliva may be of significance in countering the destructive consequences of P. gingivalis-induced chronic mucosal How to cite this paper: Slomiany, B.L. and Slomiany, A. (2018) Proinflammatory Signaling Cascades of Periodontopathic Oral

Functional activity of the oral endothelium in persons, with chronic periodontitis during treatment with plasmolifting

“…Так, например, Porphyromonas gingivalis, связываясь с эндотелиоцитами, увеличивает экспрессию генов различных хемокинов (например, CXCL8, CCL2), молекул адгезии (CD54, CD62E, PECAM-1), ICAM-1/CD54, VCAM-1/ CD106, активирует калликреин-кининовую систему [7,8].…”

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].…”

“…The LPS-induced p38 activation and its recruitment to the cytosolic aspect of the membrane-localized Rac1 GTPase has been linked to disintegrin-metalloprotease ADAM17 activation [32] [49], and the up-regulation in MAPK and Rac activation was observed in association with LPS-induced pulmonary inflammation and TLR4-stimulated phagocytosis [51] [52]. There are also strong indications that ERK activation upon LPS stimulation plays an important role in the phosphorylation of cytosolic phospholipase A 2 (cPLA 2 ) that facilitates the enzyme translocation from cytosol to membrane to gain access to phospholipid substrates [33] [50]. Moreover, further up-regulation in cPLA 2 activation has been reported to occur with the involvement of Rac1/p38 complex [53] [54].…”

“…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.…”