Variable Cell Responses to P. gingivalis Lipopolysaccharide

Abstract

Porphyromonas gingivalis is a major etiological agent of chronic periodontal diseases, the virulence of which has been attributed to different factors, including lipopolysaccharide (LPS). We investigated the differential responses induced by P. gingivalis LPS stimulation of human umbilical vein endothelial cells and human oral epithelial cells. RT-PCR analysis showed that P. gingivalis LPS used Toll-like receptor 2 (TLR2) to activate epithelial cells and Toll-like receptor 4 (TLR4) to activate endothelial cells. Both cell types were stimulated by P. gingivalis LPS to produce pro-inflammatory cytokines. Cytokine Array assay showed that although patterns of cytokine expression were similar in both cell types, some cytokines were specifically secreted by the endothelial cells, and others were specific to epithelial cells. These results support the idea that the same LPS preparation can act as a TLR2 or TLR4 agonist, depending on TLR expression of the host cell, inducing cytokine profiles that differ according to the cell type.

Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signalling

“…However, as already mentioned, the TLR2 agonist activity in P. gingivalis is most likely due to a lipoprotein, and treatment of LPS with lipoproteinase as free LPS substantially attenuated the TLR2 engaging activity [17]. These findings explain previous observations that P. gingivalis LPS can act both as a TLR4 agonist and antagonist, with an end result of varying cytokine secretion profiles [5,11,12]. Also in HOKs, P. gingivalis LPS 1 , 690 -induced LBP expression occurred through both TLR2 and TLR4 [51], while recombinant rh LBP significantly up regulated the expression of IL-6 and IL-8 in HOKs through the TLR2 signalling pathway [50].…”

“…Hence in immunological terms, the A-LPS heterogeneous forms represent ‘pathogen associated molecular patterns’ (PAMPs) and have been extensively studied for their role in the pathogenesis of periodontitis (for a review, see Nichols et al [10]), however not without controversy. Whereas some studies reported that P. gingivalis LPS stimulates secretion of pro-inflammatory cytokines [11], others found contradictory results with regard to cytokine release [5,12]. Besides, LPS acting as an agonist for Toll-like receptor (TLR) TLR2 or as an antagonist and/or agonist for TLR4 activation [13–16] added to further contradiction.…”

Porphyromonas gingivalis Lipopolysaccharide Weakly Activates M1 and M2 Polarized Mouse Macrophages but Induces Inflammatory Cytokines

“…Previous investigations into the effect of P. gingivalis LPS on nonpolarized macrophages have shown that the induced immune responses is varied and that many cytokines were only transiently expressed compared to Escherichia coli LPS and other Gram-negative pathogens (7)(8)(9). Furthermore, P. gingivalis LPS is atypical in that it is structurally different from the canonical enterobacterial LPS and has been reported to stimulate both TLR4 and TLR2 (10)(11)(12).…”

Human Trial of Liposomal Lactoferrin Supplementation for Periodontal Disease

“…26,27) In this study, mRNA expres- sion of TLR2 or TLR4 was also analyzed using real-time RT-PCR to investigate the biological mechanisms of L-bLF supplementation on the decreased inflammatory cytokines from P. gingivalis LPS-stimulated PBMCs. However, mRNA expression levels of these receptors were not changed throughout the test period, which suggests that suppressive effect of L-bLF on LPS-induced inflammatory cytokines production from PBMCs was not due to the regulation of these receptors.…”