IGFBP-4对A549细胞免疫原性细胞死亡的作用及其机制

目的：探讨IGFBP-4对A549细胞免疫原性细胞死亡（ICD）的作用及其分子机制。方法：体外培养A549细胞，将细胞分为对照组、IGFBP-4组、IGFBP-4+NAC组和IGFBP4+si-p38组。经培养48 h后，用MTT法检测细胞存活率，流式细胞技术检测细胞内ROS、钙网蛋白（CRT）含量，ELISA法检测培养基中高迁移率族蛋白1（HMGB1）含量和细胞内SOD、MDA含量，Western blot法检测p-p38和p38表达。结果：与对照组相比，IGFBP-4组细胞内ROS、CRT、HMGB1、MDA含量、p-p38和p38表达升高，细胞存活率、SOD2含量下降（P＜0.05）；与IGFBP-4组相比，IGFBP-4+NAC组和IGFBP-4+si-p38细胞内ROS、CRT、HMGB1和MDA含量下降，细胞存活率、SOD2含量增高（P＜0.05）。结论：IGFBP-4通过激活p38 MAPK通路，诱发细胞内氧化应激促使A549细胞发生免疫原性细胞死亡。

The effect of IGFBP-4 treatment on immunogenic cell death in A549 cells and its mechanism

Objective: To investigate the effect of IGFBP-4 treatment on immunogenic cell death in A549 cells and its molecular mechanism. Methods: A549 cells were cultured in vitro and assigned to the control group, IGFBP-4 group, IGFBP-4+NAC group and IGFBP4+si-p38 group, respectively. After 48 hours, MTT was used to detect the survival rate of cells; flow cytometry was used to detect ROS content and calreticulin (CRT); ELISA was used to detect HMGB1 in medium and SOD and MDA in cells; Western blot was used to analyzed the expression of phosphorylated p38 (p-p38) and total p38. Results: Compared with control group, the content of ROS, CRT, HMGB1, MDA, the expression of p-p38 and p38 increased, while the survival rate and content of SOD2 decreased in IGFBP-4 group (P<0.05). Compared with IGFBP-4 group, the content of ROS, CRT, HMGB1, MDA decreased, while the survival rate and content of SOD2 increased in IGFBP4+NAC group and IGFBP4+si-p38 group (P<0.05). Conclusion: IGFBP-4 promoted immunogenic cell death via activating p38 MAPK signaling and inducing oxidative stress in A549 cells.