Li Haobo, Yuan Shuai, Yue Zhipeng, Zhang Lei, Chen Shu, Qian Qirong, Fu Qiwei, Chen Yi
Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai, 200003 China.
Cytotechnology. 2025 Apr;77(2):52. doi: 10.1007/s10616-024-00695-2. Epub 2025 Jan 31.
Our study probed into how curcumin modulates NF-κB pathway to regulate articular chondrocytes. ATDC5 cells were exposed to varying concentrations of curcumin (0, 10, 20, 50, or 100 μM) for 48 h, followed by an assessment of curcumin's cytotoxicity. Cells were also treated with 10 ng/ml IL-1β, curcumin, 5 μg/L NF-κB inhibitor (PDTC), and 5 μM NLRP3 inflammasome inducer (nigericin) for 48 h, before cell viability, apoptosis, NF-κB pathway-related proteins, NLRP3 inflammasome-related proteins and inflammatory cytokines were detected. IL-1β treatment notably diminished chondrocyte viability and increased apoptosis, evidenced by elevated level of Bax and cleaved caspase-3, and reduced level of Bcl2, while such expression patterns were reversed by curcumin treatment in a concentration-dependent fashion. Additionally, NF-κB pathway and NLRP3 inflammasome in chondrocytes were activated by IL-1β treatment, but can also be suppressed following curcumin intervention. Furthermore, inhibition of NF-κB pathway curtailed the NLRP3 inflammasome activation and chondrocyte apoptosis, while activation of the NLRP3 inflammasome partially reversed the protective impacts of curcumin against chondrocyte apoptosis. Curcumin inhibits NF-κB pathway, thereby preventing the NLRP3 inflammasome activation and ameliorating IL-1β-induced apoptosis in articular chondrocytes.
我们的研究探讨了姜黄素如何调节核因子-κB(NF-κB)信号通路以调控关节软骨细胞。将ATDC5细胞暴露于不同浓度的姜黄素(0、10、20、50或100 μM)中48小时,随后评估姜黄素的细胞毒性。细胞还分别用10 ng/ml白细胞介素-1β(IL-1β)、姜黄素、5 μg/L NF-κB抑制剂(PDTC)和5 μM NLRP3炎性小体激活剂(尼日利亚菌素)处理48小时,然后检测细胞活力、细胞凋亡、NF-κB信号通路相关蛋白、NLRP3炎性小体相关蛋白和炎性细胞因子。IL-1β处理显著降低了软骨细胞活力并增加了细胞凋亡,表现为Bax和裂解的半胱天冬酶-3水平升高以及Bcl2水平降低,而姜黄素处理以浓度依赖的方式逆转了这种表达模式。此外,IL-1β处理激活了软骨细胞中的NF-κB信号通路和NLRP3炎性小体,但姜黄素干预后也可被抑制。此外,抑制NF-κB信号通路可减少NLRP3炎性小体的激活和软骨细胞凋亡,而激活NLRP3炎性小体则部分逆转了姜黄素对软骨细胞凋亡的保护作用。姜黄素抑制NF-κB信号通路,从而防止NLRP3炎性小体激活,并改善IL-1β诱导的关节软骨细胞凋亡。