Guanghua School of Stomatology & Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Ling Yuan Xi Road, Guangzhou 510055, China.
Int J Mol Sci. 2019 Apr 24;20(8):2023. doi: 10.3390/ijms20082023.
Tet-eleven translocation 1 (TET1) is a dioxygenase that plays an important role in decreasing the abundance of DNA methylation and changing the expression levels of specific genes related to inflammation. (Pg.) lipopolysaccharide (LPS) can induce periodontal diseases that present with severe bone loss and collagen fiber destruction accompanied by a high number of M1 macrophages. M1-polarized macrophages are pivotal immune cells that promote the progression of the periodontal inflammatory response, but the function of TET1 during M1 macrophage activation is still unknown. Our results showed that the mRNA and protein expression levels of TET1 decreased in THP-1 cells during M1 macrophage differentiation. knockdown resulted in a significant decrease in the production of proinflammatory markers such as IL-6, TNF-α, CCL2, and HLA-DR in Pg. LPS/IFN-γ- and () LPS/IFN-γ-induced M1 macrophages. Mechanistically, knockdown downregulated the activity of the NF-κB signaling pathway. After treatment with the NF-κB inhibitor BAY 11-7082, M1 marker expression showed no significant difference between the knockdown group and the control group. Taken together, these results suggest that depletion inhibited Pg. LPS/IFN-γ-induced M1 macrophage polarization through the NF-κB pathway in THP-1 cells.
Tet-eleven 易位蛋白 1（TET1）是一种双加氧酶，在降低 DNA 甲基化丰度和改变与炎症相关的特定基因表达水平方面发挥重要作用。脂多糖（LPS）可诱导牙周病，表现为严重的骨丧失和胶原纤维破坏，并伴有大量 M1 巨噬细胞。M1 极化的巨噬细胞是促进牙周炎症反应进展的关键免疫细胞，但 TET1 在 M1 巨噬细胞激活中的功能尚不清楚。我们的研究结果表明，在 M1 巨噬细胞分化过程中，THP-1 细胞中 TET1 的 mRNA 和蛋白表达水平降低。 敲低导致 Pg. LPS/IFN-γ-和 () LPS/IFN-γ 诱导的 M1 巨噬细胞中促炎标志物如 IL-6、TNF-α、CCL2 和 HLA-DR 的产生显著减少。机制上， 敲低下调了 NF-κB 信号通路的活性。用 NF-κB 抑制剂 BAY 11-7082 处理后， 敲低组和对照组 M1 标志物表达无显著差异。综上所述，这些结果表明， 在 THP-1 细胞中， 通过 NF-κB 通路抑制 Pg. LPS/IFN-γ 诱导的 M1 巨噬细胞极化。
