歯髄細胞の自然免疫反応におけるIDO 誘導を介したIFN-γ の調節的役割

In the progression of pulpitis, marked infiltration of inflammatory cells such as activated T cells producing interferon-γ (IFN-γ) is observed. Indoleamine 2, 3-dioxygenase (IDO) is a regulator of immune responses and the IDO expression is induced by IFN-γ in a variety of cells, whose expression in dental pulp is unknown. Dental pulp cells have a capacity to produce various pro-inflammatory cytokines through microbial pattern recognition receptors (PRRs) such as toll-like receptors (TLRs) or nucleotide-binding oligomerization domain (NOD) like receptors. We hypothesized that IFN-γ can modulate immune response to PRRs ligands on the dental pulp cells. The purpose of this study was to determine the role of IFN-γ in the innate immune response on production of pro-inflammatory cytokines such as C-X-C motif chemokine 10 (CXCL10) and interleukin (IL)-6 and IDO expression in cultured human dental pulp cells (HDPC). Enzyme-linked immunosorbent assay revealed that IFN-γ significantly up-regulated CXCL10 and IL-6 production in the HDPC stimulated with ligands for PRRs such as TLR2, TLR4, NOD1 and NOD2 in a concentration-dependent manner. Immunohistochemistry demonstrated expression of IDO in inflamed pulp tissue. In addition, IFN-γ in combination with the PRR ligands enhanced IDO expression in the HDPC compared with IFN-γ alone. Moreover, CXCL10 production in IFN-γ-stimulated HDPC was inhibited by an IDO inhibitor. Taken together, this study demonstrated the synergistic effects by IFN-γ on CXCL10 and IL-6 production and expression of IDO in HDPC. These findings suggest that IFN-γ may modulate the innate immune response of dental pulp cells.