Lipopolysaccharide fromPorphyromonas GingivalisStimulates Rat Mast Cells to Cysteinyl Leukotriene Generation and Upregulates Toll-like Receptor −2 and −4 Expression

Abstract

Mast cells are found in all tissues of the oral cavity and it is suggested that they take part in the development of oral inflammation. As Porhyromonas gingivalis is widely recognized as a major pathogen in the development and progression of gingivitis and periodontitis, the aim of our study is to determine the effect of P. gingivalis lipopolysaccharide (LPS) on mast cell degranulation, cysteinyl leukotriene (cysLT) generation, and migration, as well as Toll-like receptor (TLR)-2 and -4 expression. Experiments were carried out in vitro on rat peritoneal mast cells. LPS-induced mast cell histamine release was estimated by a spectrofluorometric method and cysLT generation by ELISA test. Mast cell migration in response to this antigen was examined according to Boyden's modified method and TLR expression was determined by flow cytometry. We found that P. gingivalis LPS did not induce mast cell degranulation and histamine release. However, activation of mast cells with this bacterial antigen resulted in generation and release of significant amounts of cysLTs. We also documented that LPS from P. gingivalis did not stimulate mast cell migration, even in the presence of laminin, whereas it strongly upregulated TLR2 and TLR4 expression on mast cells. Observations that P. gingivalis LPS activates mast cells to generate and release proinflammatory mediators such as cysLTs and modulates TLR2 and TLR4 expression indicates that these cells might be involved in the emergency of inflammatory processes evolved in response to P gingivalis infection.

Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide

“…To determine the specificity of PgLPS 1690 for HDPs, we tested its effect on Ca 2ϩ mobilization induced by C3a. While PgLPS 1690 inhibited Ca 2ϩ responses to HDPs, it had no effect on the response to C3a ( Mast cells express TLR2 and TLR4, key receptors for LPS recognition, yet previous studies have shown that PgLPS does not induce degranulation in rat peritoneal mast cells (55). Similarly, we found that PgLPS 1690 and PgLPS 1435/1449 did not cause degranulation in human LAD2 cells ( Fig.…”

Bradykinin promotes Toll like receptor-4 expression in human gingival fibroblasts

“…It is also known that in response to treatment with lipoteichoic acid, LPS, poly(I:C) and flagellin induce expression of IL-8 by coupling with the respective receptors TLR 2, 3, 4 and 5 [32,33]. Likewise, it has been demonstrated that purified preparations of LPS obtained from P. gingivalis stimulate receptors TLR 2 and TLR4 [34]. The effect on expression of these receptors is of great importance, since the pathogen-associated molecular patterns present in dental plaque participate in inducing expression of inflammatory cytokines [35].…”

Expression of surface and intracellular Toll-like receptors by mature mast cells

“…Only TLR2, TLR3, and TLR4 proteins were found in mast cells from isolated human nasal polyps [22], murine peritoneal cavity [38], and FSMC [30]. Our previous studies have shown that freshly isolated rat peritoneal mast cells express both surface TLR2 and TLR4 molecules [20, 39], as well as TLR3 and TLR7 surface proteins [40, 41]. In this study we evaluated the expression of TLR receptors in native fully mature rat mast cells freshly isolated from the peritoneal cavity, that is connective tissue type mast cells.…”