Table 3.
Protease activated receptors (PAR) targeted by gingipains and the consequence of their activation
| Targeted cells | Targeted PAR / gingipain | Response to PAR signaling | Pathophysiological consequence | Ref. |
|---|---|---|---|---|
| Neutrophils | PAR-2 Rgp | Increase in the intracellular Ca2+ concentration | Neutrophil activation | (112) |
| Osteoblasts | PAR-2 Rgp | Increase in the intracellular Ca2+ concentration | Activation of osteoblast-mediated osteoclastic bone resorption | (2) |
| Platelets | PAR-1, -4 RgpA, RgpB | Platelets aggregation | A putative link between periodontitis and cardiovascular disease | (114) |
| Oral epithelial cells | PAR-1, -2 | Stimulation of interleukin-6 expression | Inflammatory events associated with periodontal disease | (113) |
| Platelets | PARs Rgp enriched vesicles | Platelets aggregation | As above | (166) |
| Pulp cells | PAR-2 RgpB | Induced expression of neuropeptides: calcitonin gene-related peptide (CGRP) and substance P (SP) | A putative link between periodontitis and pulp inflammation | (217) |
| Gingival fibroblasts | PAR-1, -2 Rgp | Induced expression of hepatocyte growth factor | Effect on both inflammatory and tissue reparative processes | (220) |
| Rat kidney epithelial cells | PAR-2 P. gingivalis culture supernatants | Ca2+ mobilization | (61) | |
| Keratinocytes | PAR-1, -2 Rgp | Up-regulation of HIV-1 co receptor CCR5 | Promotion of HIV infection of oral keratinocytes | (43) |
| Oral epithelial cells | PAR-2 Rgp | Induced expression of human β-defensins-2 and CC chemokine ligand 20 (CCL20) | Enhancement of mucosal antibacterial defense | (31) |
| T cells | PAR-1, -2, -4 RgpA | Induced expression of CD25 and CD65 | T cell activation | (237) |
| Vascular endothelial cells | PAR RgpA | Weibel-Palade body exocytosis, enhanced production of interleukin-8 in response to lipopolysaccharide | Enhanced proinflammatory responses to P. gingivalis | (76) |
| Oral epithelial cells | PAR-1, -2 Rgp, Kgp | RgpB upregulate while Kgp and RgpA downregulate interleukin-8 expression | Attenuation of neutrophils migration and sustained chronic inflammation | (221) |
| Monocytic THP-1 cells | PARs Rgp, Kgp | Up-regulation of pro-inflammatory cytokines (interleukin-6, interleukin-8 and monocyte chemoattractant protein-1) | Synergistic effect of PAR-dependent and PAMPs receptor (Toll-like receptors or NOD1/2) signaling resulting in enhancement of mucosal antibacterial defense | (219) |
| ST2 mouse stromal cells and calvarial osteoblasts | PAR P. gingivalis cells | Proinflammatory responses independent of the Toll-like receptor/MyD88 pathway | Pathogen recognition: enhancement of mucosal antibacterial defense | (148) |
| Platelets | PARs Rgps | Platelet sensitization to aggregation by the stress hormone epinephrine | Mechanistic explanation of a direct connection between periodontitis and stress | (139) |
| Human oral keretinocytes | PAR-1, -2 P. gingivalis cells | PAR-1 cleavage by Rgps mediated up-regulation of pro-inflammatory cytokines (interleukin-1α, interleukin-1β, interleukin-6, tumor necrosis factor-α) | Osteoclasts differentiation and alveolar bone resorption | (42) |