%0 Journal Article
%T IWP-2 modulates the immunomodulatory properties of human dental pulp stem cells in vitro.
%A Chansaenroj A
%A Kornsuthisopon C
%A Suwittayarak R
%A Rochanavibhata S
%A Loi LK
%A Lin YC
%A Osathanon T
%J Int Endod J
%V 57
%N 2
%D 2024 Feb
%M 37971040
%F 5.165
%R 10.1111/iej.14001
%X OBJECTIVE: To investigate the effect of IWP-2, Wnt inhibitor, on human dental pulp stem cells (hDPSCs) responses.
METHODS: hDPSCs were isolated from human dental pulp tissues. Cells were treated with 25 μM IWP-2 for 24 h, and subsequently, the gene expression profile was examined using high-throughput RNA sequencing. The mRNA expression was analysed using qPCR. The effect of IWP-2 was investigated in both normal and LPS-induced hDPSCs (inflamed hDPSCs). CD4+ T cells and CD14+ monocyte-derived macrophages were cultured with conditioned media of IWP-2 treated hDPSCs to observe the immunosuppressive property.
RESULTS: RNA sequencing indicated that IWP-2 significantly downregulated several KEGG pathways, including cytokine-cytokine receptor interaction, IL-17 signalling pathway, and TNF signalling pathway. In both normal and inflamed conditions, IWP-2 markedly upregulated TGFB1 mRNA expression while the mRNA expression of pro-inflammatory cytokines, TNFA, IL1B, IFNG, and IL6, was inhibited. In the inhibition experiment, the pretreatment with p38, MAPK, or PI3K inhibitors abolished the effects of IWP-2 in LPS-induced inflammation. In terms of immune cells, IWP-2-treated-inflamed hDPSCs conditioned media attenuated T cell proliferation and regulated regulatory T cell differentiation. In addition, the migratory property of macrophage was decreased after being exposed to IWP-2-treated inflamed hDPSCs conditioned media.
CONCLUSIONS: IWP-2 suppressed inflammatory cytokine expression in both normal and inflamed hDPSCs. Moreover, hDPSCs exerted the immunosuppressive property after IWP-2 treatment. These results suggest the role of Wnt in inflammatory responses and immunomodulation in dental pulp tissues.