Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
Clin Oral Investig. 2023 Jun;27(6):2875-2885. doi: 10.1007/s00784-023-04885-8. Epub 2023 Feb 3.
This study aims to investigate the anti-inflammatory effect of curcumin and underlying mechanisms regarding the modulation of the nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome in human dental pulp stem cells (hDPSCs).
The impact of curcumin on the viability of hDPSCs was evaluated. The effect of curcumin on the expression of IL-1β and NLRP3 in hDPSCs stimulated by lipopolysaccharide (LPS) was assessed. Then, LPS-primed hDPSCs were pre-treated with curcumin before ATP triggering NLRP3 inflammasome activation, and NLRP3 inflammasome-related mediators were assessed. The mechanism of curcumin inactivation of LPS plus ATP-induced inflammasome associated with NF-κB pathway was explored. The NF-κB pathway related pro-inflammatory mediators at mRNA and protein levels were evaluated. The expression of NF-κB p65 and phosphorylation p65 was visualized after curcumin or NF-κB inhibitor administrating respectively in hDPSCs with an activated NLRP3 inflammasome. Statistical analysis was performed.
While curcumin at the concentration of 0.5-5 μM showed no obvious impact on the viability of hDPSCs, it significantly decreased IL-1β and NLRP3 mRNA expression in LPS-induced hDPSCs in a dose-dependent manner. Curcumin significantly inhibited the LPS plus ATP-primed NLRP3 inflammasome activation in hDPSCs (NLRP3, ASC, caspase-1, and IL-1β). Curcumin evidently attenuated the LPS plus ATP-induced expression of NF-κB pathway-related pro-inflammatory mediators (IL-6, IL-8, TNF-α, and COX-2). Furthermore, curcumin effectively reduced p65 phosphorylation, which acts as an NF-κB inhibitor in hDPSCs with an activated NLRP3 inflammasome.
Curcumin pre-treatment may exert an anti-inflammatory role via inactivation of the NLRP3 inflammasome by inhibiting NF-κB p65 phosphorylation in cultured hDPSCs.
Curcumin may have therapeutic potential in pulp inflammation.
本研究旨在探讨姜黄素对人牙髓干细胞（hDPSCs）中核苷酸结合寡聚化结构域样受体热蛋白结构域 3（NLRP3）炎性体的调节作用及其抗炎机制。
评估姜黄素对 hDPSCs 活力的影响。检测姜黄素对脂多糖（LPS）刺激的 hDPSCs 中白细胞介素-1β（IL-1β）和 NLRP3 表达的影响。然后，在 LPS 预刺激 hDPSCs 触发 NLRP3 炎性体激活之前，用姜黄素进行预处理，并评估 NLRP3 炎性体相关介质。探讨姜黄素失活 LPS 加 ATP 诱导的与 NF-κB 通路相关的炎性体的机制。评估 NF-κB 通路相关促炎介质在 mRNA 和蛋白水平的表达。在激活的 NLRP3 炎性体的 hDPSCs 中分别用姜黄素或 NF-κB 抑制剂处理后，观察 NF-κB p65 及其磷酸化 p65 的表达。进行统计分析。
姜黄素浓度为 0.5-5 μM 时，对 hDPSCs 的活力无明显影响，但呈剂量依赖性显著降低 LPS 诱导的 hDPSCs 中 IL-1β 和 NLRP3 mRNA 表达。姜黄素显著抑制 LPS 加 ATP 预刺激的 hDPSCs 中 NLRP3 炎性体的激活（NLRP3、ASC、半胱天冬酶-1 和 IL-1β）。姜黄素明显减弱 LPS 加 ATP 诱导的 NF-κB 通路相关促炎介质（IL-6、IL-8、TNF-α 和 COX-2）的表达。此外，姜黄素有效降低 p65 磷酸化，这在激活的 NLRP3 炎性体的 hDPSCs 中作为 NF-κB 抑制剂发挥作用。
姜黄素预处理可能通过抑制 NF-κB p65 磷酸化来抑制 NLRP3 炎性体的激活，从而发挥抗炎作用。
姜黄素可能具有治疗牙髓炎症的潜力。
