Porphyromonas gingivalis and its lipopolysaccharide differently modulate epidermal growth factor–dependent signaling in human gingival epithelial cells

Abstract

Periodontitis is an inflammatory disease induced by pathogenic bacteria such as Porphyromonas gingivalis. Little is known about epidermal growth factor (EGF) signals in human gingival epithelial cells (HGEC), which are major targets of P. gingivalis, and how the expression of proteins participating in EGF signaling—that is, EGF-receptor (EGFR), suppressor of cytokine signaling-3 (SOCS-3), interferon regulatory factor-1 (IRF-1), and signal transducers and activators of transcription (STAT-3)—are modified. This study aimed to assess the effects of P. gingivalis and its purified lipopolysaccharide (LPS-Pg) on EGF signaling. HGEC were infected for 2 h in a dose-dependent manner with P. gingivalis and with heat-killed P. gingivalis, and activated for 2 and 24 h by 1 µg/mL of purified LPS-Pg. Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to measure mRNA and protein levels for SOCS-3, IRF-1 EGF, EGFR, and STAT-3. The tyrosine-phosphorylation status of STAT-3 was also examined. The results showed that infection of HGEC cells with P. gingivalis, but not with heat-killed P. gingivalis, led to significant reductions in expression levels of mRNAs and proteins for SOCS-3, IRF-1, and EGFR, while LPS-Pg over time significantly increased the expression of these mRNAs and proteins. Tyrosine-phosphorylation of STAT-3 was significantly increased during infection with P. gingivalis and activation by LPS-Pg but not modified during infection with heat-killed P. gingivalis. This study highlights that P. gingivalis and its purified LPS differentially modulated the expression of proteins (SOCS-3, IRF-1, EGFR, and STAT-3) interfering with EGF signaling.

Gelatin nonwovens‐based epithelial morphogenesis involves a signaling axis comprising EGF‐receptor, MAP kinases ERK 1/2, and β1 integrin

“…It is evidenced by the multitude of reports that the signaling, which emerges from growth factor receptor activation upon ligand binding, is crucial for tissue development, including stratified epithelia like skin or oral mucosal gingiva . In this context, we first analyzed the expression of the EGF‐R, one of the most extensively studied receptors in human tissues .…”

“…It is evidenced by the multitude of reports that the signaling, which emerges from growth factor receptor activation upon ligand binding, is crucial for tissue development, including stratified epithelia like skin or oral mucosal gingiva. 24,25 In this context, we first analyzed the expression of the EGF-R, one of the most extensively studied receptors in human tissues. 26 Figure 1 visualizes the expression and the topology of the EGF-R during epithelial morphogenesis by employing IIF with antibodies, truly detecting the total EGF-R protein (EGF-R tp ), and its phosphorylation at the srcspecific site EGF-R T845 .…”

Identification of novel key lncRNAs involved in periodontitis by weighted gene co‐expression network analysis

“…The biological process enrichment of LBX2‐AS1 showed that neutrophil activation involved in immune response might play an important role in periodontitis and LBX2‐AS1 might be vital to neutrophil‐mediated immunity. Interestingly, increasing studies showed that JAK‐STAT, EGFR, phosphatidylinositol and VEGF signalling pathway were associated with periodontitis . Wang et al found that 25‐OHD3 could improve diabetic periodontitis via downregulation of JAK1/STAT3 signalling in the gingival epithelium .…”

“…While Zheng et al reported that plumbagin suppressed chronic periodontitis progression in rats by inhibiting the MAPK, NF‐κB and JAK/STAT signalling pathways . Besides, researchers showed that infection of human gingival epithelial cell with Porphyromonas gingivalis led to significant reductions in expression levels of EGFR . Interestingly, P. gingivalis could attenuate the PI3K/Akt signalling pathway via the proteolytic effects of gingipains, resulting in the dysregulation of PI3K/Akt‐dependent cellular functions and the destruction of epithelial barriers .…”

Effect of scaling and root planing on level of immunoglobulin E and immunoglobulin G4in children with gingivitis and house-dust mite allergy: A pilot randomised controlled trial

“…45 Previous studies demonstrated the pathogenic role of Pg dental biofilm to stimulate LPS-driven inflammatory responses, 46 and therefore, lack of dental plaque and calculus in supra-gingival surface, sub-gingival surface and human epithelial cell rests of Malassez accounted for the lack of response to LPS to induce sensitisation of atopic inflammatory responses. 47,48 Moreover, given the unique LPS-induced atopic inflammatory responses, we can control atopic inflammatory responses by removing dental biofilm. This reduces the subject body's load of LPS-triggered mast cells derived from periodontal inflammation.…”