Inducing cyclooxygenase-2 expression, prostaglandin E 2 and prostaglandin F 2α 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.

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 E2 (PGE2 ) and PGF2α 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. PGE2 and PGF2α 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 PGE2 and PGF2α production of HDPCs. Poly (I:C) activated p -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 PGE2 and PGF2α 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 PGE2 and PGF2α production, contributing to the pathogenesis and progression of pulpal/periapical diseases.