Soluble CD14 Enhances the Response of Periodontal Ligament Stem Cells to P. gingivalis Lipopolysaccharide

Andrukhov, Oleh; Andrukhova, Olena; Özdemir, Burcu; Haririan, Hady; Müller-Kern, Michael; Moritz, Andreas; Rausch‐Fan, Xiaohui

doi:10.1371/journal.pone.0160848

Cited by 40 publications

(65 citation statements)

References 52 publications

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“…Interestingly, our previous studies show that the response of hPDLSCs to TLR‐4 agonist E. coli LPS is substantially (up to 10‐fold) lower compared with that of Pam3CSK4, although TLR‐4 receptors uses both MyD88‐dependent and MyD88‐independent signaling . This observation is quite surprising, because in the present study we showed that simultaneous activation of MyD88‐dependent and MyD88‐independent pathway leads to synergistic effects on IL‐6, IL‐8, and MCP‐1 production.…”

Section: Discussioncontrasting

confidence: 40%

Synergistic effects triggered by simultaneous Toll‐like receptor‐2 and ‐3 activation in human periodontal ligament stem cells

Blufstein

Behm

Gahn

et al. 2019

Journal of Periodontology

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BackgroundAlthough periodontitis is associated with disruption of the host‐microbial homeostasis, viruses are currently discussed to influence disease progression. Viral pathogens are recognized by Toll‐like receptor (TLR)‐3, which engages a different signaling pathway than other TLRs. This study aimed to investigate the effect of TLR‐3 agonist polyinosinic:polycytidylic acid (Poly I:C) on the expression of inflammatory markers and bone metabolism proteins by human periodontal ligament stem cells (hPDLSCs) compared with TLR‐2 agonist Pam3CSK4, which mimics the effect of bacterial lipoproteins. To assess potential combined effects of bacterial and viral infections, hPDLSCs response to simultaneous TLR‐2 and TLR‐3 activation was investigated.MethodsHPDLSCs were stimulated with Poly I:C (0.0001‐1 µg/mL), Pam3CSK4 (1 µg/mL), and their combinations for 24 hours. Gene expression and protein levels of interleukin (IL)‐6, IL‐8, monocyte chemoattractant protein (MCP)‐1, and osteoprotegerin (OPG) were measured with qPCR and ELISA.ResultsProduction of IL‐6, IL‐8, MCP‐1, and OPG was significantly increased by Poly I:C or Pam3CSK4 to a similar extent. The levels of all inflammatory mediators induced by simultaneous stimulation with Poly I:C and Pam3CSK4 were significantly higher compared with single stimuli as well as to their summed response. Gene expression and protein levels of OPG were enhanced by Poly I:C, but by lesser extent than by Pam3CSK4. OPG levels upon simultaneous stimulation with Pam3CSK4 and Poly I:C were significantly lower compared with Pam3CSK4 stimulation alone.ConclusionsSimultaneous TLR‐2 and TLR‐3 activation synergistically triggers IL‐6, IL‐8, and MCP‐1 production, which was not observed for OPG. These findings suggest that TLR‐3 activation by viral infections might promote periodontitis progression.

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Section: Discussioncontrasting

confidence: 40%

Synergistic effects triggered by simultaneous Toll‐like receptor‐2 and ‐3 activation in human periodontal ligament stem cells

Blufstein

Behm

Gahn

et al. 2019

Journal of Periodontology

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“…For this reason, the response to TLR2/1 agonist Pam3CSK4 and TLR4 agonist E. coli LPS was compared between pretreated and non‐pretreated cells. Additionally, both P. gingivalis LPS and E. coli LPS were administered together with sCD14 in a physiologically relevant concentration …”

Section: Discussionmentioning

confidence: 99%

“…The expression of TLR2 and TLR4 is altered in periodontal disease and therefore these receptors are discussed to play an important role in disease progression . TLR4 activation by different bacterial LPS induces the production of inflammatory mediators in hPDLCs . Similarly, TLR2 activation results in cytokine production by PDLs and gingival fibroblasts …”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, some hPDLCs were pretreated with P. gingivalis LPS (0.1 or 0.3 μg/mL) in the presence of soluble CD14 (250 ng/mL) in serum‐free DMEM supplemented with 1% penicillin/streptomycin. As shown by our recent study and preliminary data, stimulation with such P. gingivalis LPS concentrations result in a submaximal response in hPDLCs . Another group of hPDLCs did not get any treatment and were incubated with serum‐free DMEM with 1% penicillin/streptomycin alone.…”

Section: Methodsmentioning

confidence: 96%

“…In addition, in this study stimulation with LPS was performed in the absence of soluble CD14 (sCD14). It is known that hPDLCs lack of membrane bound CD14 protein and sCD14 significantly enhances the response of these cells to bacterial LPS . Moreover, sCD14 is present in saliva and gingival crevicular fluid and therefore its application in experiments with LPS reflects physiological conditions more adequately …”

Section: Introductionmentioning

confidence: 99%

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Human periodontal ligament cells exhibit no endotoxin tolerance upon stimulation with Porphyromonas gingivalis lipopolysaccharide

Blufstein

Behm

Nguyen

et al. 2018

J of Periodontal Research

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Background/ObjectivesEndotoxin tolerance is characterized by a state of hyporesponsiveness after confrontation with endotoxins such as lipopolysaccharides (LPS) at low concentrations. The aim of this study was to investigate, whether pretreatment with Porphyromonas gingivalis leads to endotoxin tolerance induction and possible alterations in toll‐like receptor (TLR) 2‐ and 4‐induced response in human periodontal ligament cells (hPDLCs).Material and MethodsPrimary hPDLCs were pretreated with P. gingivalis (0.1 or 0.3 μg/mL) LPS for 24 hours and afterwards treated with one of the following stimuli: P. gingivalis LPS (1 μg/mL); TLR4 agonist Escherichia coli LPS (0.1 μg/mL; 1 μg/mL); TLR2 agonist Pam3CSK4 (0.1 μg/mL; 1 μg/mL). The protein expression of interleukin (IL)‐6, IL‐8 and monocyte chemotactic protein‐1 was analyzed with quantitative polymerase chain reaction and enzyme‐linked immunosorbent assay. Gene expression levels of TLR2 and TLR4 were determined by quantitative polymerase chain reaction.ResultsPretreatment of cells with low concentrations of P. gingivalis LPS did not result in lower production of IL‐6, IL‐8 and monocyte chemotactic protein‐1 compared to control group. In some cases, pretreated cells exhibited lower gene expression levels of TLR2 and TLR4 compared to non‐pretreated cells.ConclusionThe results of this study implicate that hPDLCs do not develop endotoxin tolerance. Furthermore, the amplitude of the inflammatory response shows no significant dependency on TLR2 and TLR4 expression levels.

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Porphyromonas gingivalis and dental stem cells crosstalk amplify inflammation and bone loss in the periodontitis niche

Ezhilarasan

Varghese

2022

Journal Cellular Physiology

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Periodontitis is the sixth most prevalent disease, and almost 3.5 billion people are affected globally by dental caries and periodontal diseases. The microbial shift from a symbiotic microbiota to a dysbiotic microbiota in the oral cavity generally initiates periodontal disease. Pathogens in the periodontal microenvironment interact with stem cells to modulate their regenerative potential. Therefore, this review focuses on the interaction between microbes and stem cells in periodontitis conditions. Microbes direct dental stem cells to secrete a variety of pro‐inflammatory cytokines and chemokines, which increase the inflammatory burden in the damaged periodontal tissue, which further aggravates periodontitis. Microbial interaction also decreases the osteogenic differentiation potential of dental stem cells by downregulating alkaline phosphatase, runt‐related transcription factor 2, type 1 collagen, osteocalcin, osteopontin, and so on. Microbe and stem cell interaction amplifies pro‐inflammatory cytokine signaling in the periodontitis niche, decreasing the osteogenic commitment of dental stem cells. A clear understanding of microbial stem cell interactions is crucial in designing regenerative therapies using stem cells in the management of periodontitis.

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Soluble CD14 Enhances the Response of Periodontal Ligament Stem Cells to P. gingivalis Lipopolysaccharide

Cited by 40 publications

References 52 publications

Synergistic effects triggered by simultaneous Toll‐like receptor‐2 and ‐3 activation in human periodontal ligament stem cells

Synergistic effects triggered by simultaneous Toll‐like receptor‐2 and ‐3 activation in human periodontal ligament stem cells

Human periodontal ligament cells exhibit no endotoxin tolerance upon stimulation with Porphyromonas gingivalis lipopolysaccharide

Porphyromonas gingivalis and dental stem cells crosstalk amplify inflammation and bone loss in the periodontitis niche

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