Porphyromonas gulae lipopolysaccharide elicits inflammatory responses through toll‐like receptor 2 and 4 in human gingivalis epithelial cells

Abstract

Porphyromonas gulae, a Gram‐negative black‐pigmented anaerobe, has been associated with periodontal disease in companion animals and its virulence has been attributed to various factors, including lipopolysaccharide (LPS), protease and fimbriae. Toll‐like receptors (TLRs) recognise pathogen‐associated molecular patterns, such as peptidoglycan, lipids, lipoproteins, nucleic acid and LPS. Following P. gulae infection, some inflammatory responses are dependent on both TLR2 and TLR4. In addition, a recent clinical study revealed that acute and persistent inflammatory responses enhance the expressions of TLR2 and TLR4 in the oral cavity. In this study, we investigated the interaction between P. gulae LPS and human gingivalis epithelial cells (Ca9‐22 cells). P. gulae LPS was found to increase TLR2 and TLR4 mRNA expressions and protein productions, and enhanced inflammatory responses, such as COX2, TNF‐ɑ, IL‐6 and IL‐8. Stimulated Ca9‐22 cells exhibited phosphorylation of ERK1/2 and p38, and their inhibitors diminished inflammatory responses, while knockdown of the TLR2 and/or TLR4 genes with small interfering RNA (siRNA) prevented inflammatory responses. Moreover, p38 and ERK1/2 phosphorylation was decreased in TLR2 and TLR4 gene knockdown cells. These findings suggest that P. gulae LPS activates p38 and ERK1/2 via TLR2 and TLR4, leading to inflammatory responses in human gingival epithelial cells.

Efficacy of FimA antibody and clindamycin in silkworm larvae stimulated with Porphyromonas gulae

“…Moreover, P. gingivalis has been shown to have the ability to invade human host cells, degrade cellular focal adhesion components, and induce apoptosis in a fimA -types-dependent manner [ 16 , 47 , 48 ]. Recent studies have noted that P. gulae organisms express several different virulence factors, including fimbriae, LPS, and trypsin-like proteases [ 3 , 7 , 49 , 50 ]. P. gulae LPS was found to induce inflammatory responses in human gingival epithelial cells, while cell viability was not affected [ 49 ].…”

“…Recent studies have noted that P. gulae organisms express several different virulence factors, including fimbriae, LPS, and trypsin-like proteases [ 3 , 7 , 49 , 50 ]. P. gulae LPS was found to induce inflammatory responses in human gingival epithelial cells, while cell viability was not affected [ 49 ]. On the other hand, P. gulae proteases have been reported to degrade host tissue components related to growth and proliferation, resulting in promotion of morphological changes [ 50 ].…”

Porphyromonas gingivalis, a bridge between oral health and immune evasion in gastric cancer

“…Moreover, Porphyromonas sp. can confer cancer cells with enhanced tumor invasion and metastatic capabilities by promoting matrix metalloproteinase 9 (MMP9), an extracellular matrix degrader, through activation of protease-activated receptor 2 (PAR2) and the ERK1/2-Ets1/3-p38 pathway ( 37 , 38 ) ( Figure 1 ).…”

Periodontopathic Microbiota and Atherosclerosis: Roles of TLR-Mediated Inflammation Response

“…On the contrary, Chukkapalli et al [ 34 ] observed that a marked reduction of aortic plaque area and intimal thickness in TLR2 −/− TLR4 −/− -, TLR2 +/− TLR4 −/− -, and TLR2 −/− TLR4 +/− -deficient mice infected with multiple periodontal pathogens compared with normal group. Inaba et al [ 35 ] found that the p38 and ERK1/2 phosphorylation, a potent activator of mitogen-activated protein kinase (MAPK) pathways acted as initiating inflammation, was decreased in TLR2 and TLR4 gene knockdown gingival epithelial cells. These results clearly demonstrated that partial or complete knockdown of gene of TLR2 and TLR4 reduces the progress of atherosclerotic plaque in infected animal models.…”

“…TLRs, the most characteristic members of pattern recognition receptors, are widely expressed in the various cell membrane or located in the cytoplasm, and the elevated levels of TLR expression in macrophages and endothelial cells of atheroma have been observed [ 66 ]. Inaba et al [ 35 ] demonstrated that P. gingivalis LPS enhanced the expression of TLR2 and TLR4 mRNA in human gingivalis epithelial cells. In vivo trial performed by Nakamura et al [ 67 ] also suggested that TLR2 might take charge for recognizing the fraction of P. gingivalis LPS and mediating mononuclear cell adhesion to the vascular endothelium.…”