The Anti‐Inflammatory Effect of Human Telomerase‐Derived Peptide on P. gingivalis Lipopolysaccharide‐Induced Inflammatory Cytokine Production and Its Mechanism in Human Dental Pulp Cells

Abstract

Porphyromonas gingivalis is considered with inducing pulpal inflammation and has lipopolysaccharide (LPS) as an inflammatory stimulator. GV1001 peptide has anticancer and anti-inflammation activity due to inhibiting activation of signaling molecules after penetration into the various types of cells. Therefore, this study examined inhibitory effect of GV1001 on dental pulp cells (hDPCs) stimulated by P. gingivalis LPS. The intracellular distribution of GV1001 was analyzed by confocal microscopy. Real-time RT-PCR was performed to determine the expression levels of TNF-α and IL-6 cytokines. The role of signaling by MAP kinases (ERK and p38) was explored using Western blot analysis. The effect of GV1001 peptide on hDPCs viability was measured by MTT assay. GV1001 was predominantly located in hDPC cytoplasm. The peptide inhibited P. gingivalis LPS-induced TNF-α and IL-6 production in hDPCs without significant cytotoxicity. Furthermore, GV1001 treatment markedly inhibited the phosphorylation of MAP kinases (ERK and p38) in LPS-stimulated hDPCs. GV1001 may prevent P. gingivalis LPS-induced inflammation of apical tissue. Also, these findings provide mechanistic insight into how GV1001 peptide causes anti-inflammatory actions in LPS-stimulated pulpitis without significantly affecting cell viability.

Lipopolysaccharide upregulates the proliferation, migration, and odontoblastic differentiation of NG2+ cells from human dental pulp in vitro

“…However, their biological characteristics in the reparative process under inflammatory microenvironment were not fully understood. LPS is usually used in the model of inflammation in vitro (Lee et al, ; Ko et al, ). To identify the proper concentration of LPS used for our study, the effect of various concentrations of LPS on the cell viability of NG2 + cells were tested.…”

“…As the main component of the bacterial membrane, lipopolysaccharide (LPS) induces defensive inflammatory responses in the pulp (Bindal et al, ). In several experiments, LPS has been used to form a model of inflammation (Lee et al, ; Ko et al, ; Lertchirakarn and Aguilar, ). Upon LPS stimulation, stem cells of dental pulp play an important role in differentiating into odontoblasts to form new dentin (Tecles et al, ; Volponi and Sharpe, ).…”

Management of deep caries and the exposed pulp

“…Numerous in vitro culture studies using DPC (Ko et al . ), purified dental pulp SC (DPSC) populations (Li et al . ) and in vivo studies (Renard et al .…”

“…Dental pulp cells (DPCs) when challenged by the presence of a carious microbial biofilm will directly respond by expressing a range of genes and proteins, promoting defensive cellular processes such as cell migration, proliferation and differentiation (Farges et al 2015). Numerous in vitro culture studies using DPC (Ko et al 2015), purified dental pulp SC (DPSC) populations (Li et al 2014) and in vivo studies (Renard et al 2016) have demonstrated changes in cellular transcription and protein expression when inflamed. Furthermore, cells cultured in mineralizing, angiogenic and neurogenic culture conditions express a range of extracellular molecules, which promote an autocrine and paracrine healing response (Duncan et al 2013, Gervois et al 2015.…”

Covalent Strategies for Targeting Messenger and Non-Coding RNAs: An Updated Review on siRNA, miRNA and antimiR Conjugates

“…Initially, this peptide was used for stimulating an immune response against several cancers in an injectable cancer vaccine and is currently found under clinical studies [ 48 , 49 , 50 ]. In addition to exhibiting potent anti-cancer activities as a drug, other important biological activities have been reported (e.g., antioxidant [ 51 ], anti-inflammatory [ 52 , 53 ] and antiviral [ 54 ]). Recently, the use of GV1001 have been reported as protection of stem cells by mimicking hTERT protein [ 55 ] Lee et al studied and characterized the cell entry mechanism of the peptide GV1001 [ 56 ].…”