MyD88/ERK/NFkB pathways and pro-inflammatory cytokines release in periodontal ligament stem cells stimulated by Porphyromonas gingivalis

Abstract

The present study was aimed at investigating whether human Periodontal Ligament Stem Cells (hPDLSCs) were capable of sensing and reacting to lipopolysaccharide from Porphyromonas gingivalis (LPS-G) which is widely recognized as a major pathogen in the development and progression of periodontitis. At this purpose hPDLCs were stimulated with 5 μg/mL LPS-G at various times and the expression of toll-like receptor 4 (TLR4) was evaluated. Toll-like receptors (TLRs) play an essential role in innate immune signaling in response to microbial infections, and in particular TLR4, type-I transmembrane proteins, has been shown recognizing LPS-G. Our results put in evidence, in treated samples, an overexpression of TLR4 indicating that, hPDLSCs express a functional TLR4 receptor. In addition, LPS-G challenge induces a significant cell growth decrease starting from 24 h until 72 h of treatment. LPS-G leads the activation of the TLR4/MyD88 complex, triggering the secretion of proinflammatory cytokines cascade as: IL-1α, IL-8, TNF-α and β and EOTAXIN. Moreover, the upregulation of pERK/ERK signaling pathways and NFkB nuclear translocation was evident. On the basis of these observations, we conclude that hPDLSCs could represent an appropriate stem cells niche modeling leading to understand and evaluate the biological mechanisms of periodontal stem cells in response to LPS-G, mimicking in vitro an inflammatory process occurring in vivo in periodontal disease.

TLR activation inhibits the osteogenic potential of human periodontal ligament stem cells through Akt signaling in a Myd88‐ or TRIF‐dependent manner

“…Increasing evidence suggests that TLR1‒6 are expressed in human MSCs from different origins . However, reports on TLR7‒10 are inconsistent, and to date, there are few studies reporting TLR expression in hPDLSCs . In this study, we found that TLR1, TLR3, TLR4, and TLR6 are functionally expressed at high levels, whereas the expression of TLR7, ‐8, and ‐10 is very low in hPDLSCs.…”

“…However, there have been some inconsistent, and even controversial findings regarding to the roles of TLRs in MSC osteogenic differentiation . To date, there have been few studies that have characterized the expression of different TLRs and their effects on the osteogenic potential of hPDLSCs . Therefore, in this study, we explored the expression profile of TLRs, with emphasis on TLR1, TLR3, TLR4, and TLR6, which showed higher expression in hPDLSCs.…”

Astragalus polysaccharides alleviates LPS‐induced inflammation via the NF‐κB/MAPK signaling pathway

“…NF‐κB p65 protein binds to IκB protein and is present in the cytoplasm. When IECs are stimulated by external stimuli, NF‐κB kinases (IKKs) can phosphorylate the IκB family of proteins (Diomede et al, 2017), followed by ubiquitination and degradation, further phosphorylating p65 and releasing it into the nucleus, where it promotes inflammation. APS significantly reduced the expression of phosphorylated p65 mRNA and increased the expression of IκB‐α mRNA after induction of the NF‐κB signaling pathway by LPS.…”

Strontium ion attenuates lipopolysaccharide‐stimulated proinflammatory cytokine expression and lipopolysaccharide‐inhibited early osteogenic differentiation of human periodontal ligament cells

“…Neither are hPDLCs involved only in the repair and regeneration of periodontal tissue they also played a crucial role in maintaining homeostasis during the inflammatory response . It has been demonstrated that hPDLCs possess immunomodulatory properties and could produce proinflammatory and anti‐inflammatory cytokines in inflammatory microenvironments stimulated by LPS . Similarly, it has also been reported that the inflammatory microenvironment can inhibit the osteogenic differentiation of hPDLCs, resulting in impaired periodontal regeneration .…”