Effects of Interferon-γ on odontoblastic differenti- ation and mineralization of odontoblast-like cells

Introduction: Dentinogenesis is regulated by cytokines and growth factors, and modulated by alterations in the extracellular microenvironment. Dental matrix protein-1 (DMP-1), which is predominantly expressed in odontoblasts, is required during the early and late stages of odontogenesis. In the present study, we examined the involvement of proinflammatory cytokines in the expression of odontogenic markers in the rat odontoblast-like cell line KN-3. Methods: The expression of DMP-1 and p38 mitogen-activated protein kinase (MAPK) in proinflammatory cytokine-treated KN-3 cells was evaluated by immunoblot analysis. Alkaline phosphatase (ALP) activity in proinflammatory cytokine-treated KN-3 cells was measured by ALP staining and a colorimetric assay. Results: DMP-1 protein was downregulated in KN-3 cells treated with interferon-γ (IFN-γ) for 3 days, but not in interleukin-1β (IL-1β)-treated cells. The IFN-γ-induced downregulation of DMP-1 was rescued by treatment with IL-1β for 3 days. Interestingly, ALP activity was also suppressed in IFN-γtreated KN-3 cells and no significant change was induced by IL-1β treatment for 5 days. In addition, IFN-γ treatment for 3 days remarkably upregulated the phosphorylation of p38 MAPK in KN-3 cells. Conclusions: INF-γ treatment downregulated DMP-1 expression and ALP activity in KN-3 cells through prolonged phosphorylated p38 MAPK. IL-1β treatment restored these odontogenic reactions mediated by IFN-γ. Taken together, these findings suggest that IFN-γ and IL-β may be involved in the complex regulation of odontogenesis in the microenvironment of dental pulp. Rec.3/18/2015, Acc.5/24/2015, pp210-217