Inducing Cyclooxygenase-2 Expression, Prostaglandin E and Prostaglandin F Production of Human Dental Pulp Cells by Activation of Toll-like Receptor-3, Mitogen-activated Protein Kinase Kinase/extracellular Signal-regulated Kinase and P38 Signaling
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Background/purpose: Bacterial infection was the major etiology for pulpal/root canal infection. This study aimed to investigate the activation of toll-like receptor-3 (TLR) on cyclooxygenase-2 (COX-2) expression and prostaglandin E (PGE) and PGF production of human dental pulp cells (HDPCs) and associated signaling.
Materials And Methods: HDPCs were exposed to different concentrations of Poly (I:C) (a TLR3 activator). Cell viability was determined by 3- (4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and alkaline phosphatase (ALP) activity was evaluated by ALP staining. Activation of extracellular signal-regulated kinase (ERK) and p38 by Poly (I:C) was determined by immunofluorescent staining. The COX-2 protein expression was analyzed by Western blot. PGE and PGF production was measured by enzyme-linked immunosorbent assay. The mRNA expression was studied by real-time polymerase-chain reaction. Moreover, HDPCs were exposed to Poly(I:C) with/without U0126 or SB203580 treatment and analysis of COX-2 expression and prostanoid production were conducted.
Results: Poly (I:C) showed little effect on ALP activity, but decreased viability of HDPCs. It stimulated COX-2 mRNA and protein expression. Poly (I:C) induced PGE and PGF production of HDPCs. Poly (I:C) activated -ERK, and p-p38 protein expression. Treatment by U0126 (a mitogen-activated protein kinase kinase (MEK)/ERK inhibitor) and SB203580 (a p38 inhibitor) attenuated Poly (I:C)-induced COX-2 mRNA and protein expression as well as PGE and PGF production.
Conclusion: TLR3 activation is involved in the infection and inflammatory responses of pulp tissues, via MEK/ERK, and p38 signaling to mediate COX-2 expression as well as PGE and PGF production, contributing to the pathogenesis and progression of pulpal/periapical diseases.
Dental Stem Cells and Lipopolysaccharides: A Concise Review.
Rodas-Junco B, Hernandez-Solis S, Serralta-Interian A, Rueda-Gordillo F Int J Mol Sci. 2024; 25(8).
PMID: 38673923 PMC: 11049850. DOI: 10.3390/ijms25084338.