姜黄素通过抑制 NF-κB p65 磷酸化抑制 NLRP3 炎性小体激活，从而在脂多糖刺激的人牙髓干细胞中发挥保护作用。
The protective role of curcumin in human dental pulp stem cells stimulated by lipopolysaccharide via inhibiting NF-κB p65 phosphorylation to suppress NLRP3 inflammasome activation.
机构信息
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.
出版信息
Clin Oral Investig. 2023 Jun;27(6):2875-2885. doi: 10.1007/s00784-023-04885-8. Epub 2023 Feb 3.
OBJECTIVES
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).
MATERIALS AND METHODS
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.
RESULTS
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.
CONCLUSIONS
Curcumin pre-treatment may exert an anti-inflammatory role via inactivation of the NLRP3 inflammasome by inhibiting NF-κB p65 phosphorylation in cultured hDPSCs.
CLINICAL RELEVANCE
Curcumin may have therapeutic potential in pulp inflammation.
目的
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。
材料和方法
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。
结果
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。
结论
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。
临床意义
姜黄素可能具有治疗牙髓炎症的潜力。
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