Modulatory Roles of Interferon-γ through Indoleamine 2, 3-dioxygenase Induction in Innate Immune Response of Dental Pulp Cells

Introduction: Marked infiltration of inflammatory cells such as activated T cells producing interferon-gamma (IFN-gamma) is observed in severe pulpitis. However, the roles of IFN-gamma, in the innate immune response of dental pulp have not been reported. Indoleamine 2, 3-dioxygenase (IDO) is a regulator of immune responses, and the IDO expression is induced by IFN-gamma in many cells whose expression in dental pulp is unknown. The purpose of this study was to determine the role of IFN-gamma in the immune response through microbial pattern recognition receptors (PRRs) such as Toll-like receptors or nucleotide-binding oligomerization domain like receptors on the production of proinflammatory cytokines such as CXCL10 and interleukin (IL)-6 and the expression of IDO in cultured human dental pulp cells (HDPCs). Methods: HDPCs were established from explant cultures of healthy pulp tissues. CXCL10 and IL-6 production was determined using enzyme-linked immunosorbent assay. Confirmation of IDO localization in dental pulp tissues was examined using immunohistochemistry. IDO expression in HDPCs was analyzed by immunoblot. Results: IFN-gamma significantly up-regulated CXCL10 and IL-6 production in the HDPCs stimulated with ligands for PRRs in a concentration-dependent manner. The expression of IDO was detected in inflamed pulp tissue. In addition, IFN-gamma in combination with the PRR ligands enhanced 100 expression in HDPCs compared with IFN-gamma alone. Moreover, CXCL10 production in IFN-gamma stimulated HDPCs was inhibited by an IDO inhibitor. Conclusions: This study showed the synergistic effects by IFN-gamma on cytokine production and 100 expression in HDPCs, suggesting that IFN-gamma may modulate the innate immune response of dental pulp.