Prostaglandin E2 Affects Interleukin 6 and Monocyte Chemoattractant Protein 1/CCL2 Production by Cultured Stem Cells of Apical Papilla

Abstract

Introduction: Root canal treatment of immature necrotic teeth is a major challenge in current endodontics. The effect of inflammatory mediators, such as prostaglandin, on the modulation of stem cells of the apical papilla (SCAP) is not completely understood. The aim of this study was to investigate the role of prostaglandin E₂ (PGE₂) on SCAP activation by Escherichia coli lipopolysaccharide (LPS) in vitro.

Methods: SCAP cultures were established and characterized. Increasing concentrations of lipopolysaccharide (0.1-10 μg/mL) were used to investigate cyclooxygenase-2 (COX-2/PTGS2) and PGE₂ receptors (EP1-4) gene expression. Then, SCAP were treated with a COX-2 inhibitor (indomethacin) before treatment with different concentrations of LPS. The levels of the chemokine CCL2/monocyte chemoattractant protein 1 and interleukin (IL)-6 were detected in cell supernatants (24 hours) by enzyme-linked immunosorbent assay. Data analysis was performed using analysis of variance followed by the Tukey post test.

Results: The expression of COX-2 was up-regulated in the group treated with LPS at 1μg/mL compared with that in the control group. EP1-4 were detected in all experimental conditions at similar levels. SCAP treated with indomethacin presented a down-regulation in the production of LPS-induced CCL2 and the secretion of IL-6.

Conclusions: SCAP showed increased COX-2 (PTGS2) gene expression induced by LPS and a PGE₂-dependent production of IL-6 and CCL2.

Keywords: Cytokines; immature teeth; inflammation; lipopolysaccharide; stem cells of the apical papilla.