TITLE:
Proinflammatory Signaling Cascades of Periodontopathic Oral Pathogen Porphyromonas gingivalis
AUTHORS:
Bronislaw L. Slomiany, Amalia Slomiany
KEYWORDS:
P. gingivalis, Periodontal Disease, Oral Mucosa, Inflammatory Response, LPS, TLR4, Signaling Cascades
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.6 No.5,
May
23,
2018
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 inflammation that characterizes periodontitis.