{Reference Type}: Journal Article
{Title}: IWP-2 modulates the immunomodulatory properties of human dental pulp stem cells in vitro.
{Author}: Chansaenroj A;Kornsuthisopon C;Suwittayarak R;Rochanavibhata S;Loi LK;Lin YC;Osathanon T;
{Journal}: Int Endod J
{Volume}: 57
{Issue}: 2
{Year}: 2024 Feb
{Factor}: 5.165
{DOI}: 10.1111/iej.14001
{Abstract}: <B>OBJECTIVE: </B>To investigate the effect of IWP-2, Wnt inhibitor, on human dental pulp stem cells (hDPSCs) responses.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.