Xiong Wei, Chen Hua, Lu Jiequan, Ren Jie, Nie Chen, Liang Ruijuan, Liu Feng, Huang Baofeng, Luo Yu
Department of Emergency, Shenzhen People's Hospital Longhua Branch, The Second Affiliated Hospital of Jinan Medical College, Shenzhen, China.
Department of Emergency, Shenzhen People's Hospital, The Second Affiliated Hospital of Jinan Medical College, Shenzhen, China.
Folia Histochem Cytobiol. 2021;59(3):195-202. doi: 10.5603/FHC.a2021.0019. Epub 2021 Sep 20.
The cytokine interleukin (IL)-39 is a novel member of the IL-12 family. Our previous study found that the serum level of IL-39 significantly increased in patients with acute myocardial infarction. However, the role of IL-39 in cardiomyocyte apoptosis remains unclear.
In this study, the cultured mouse HL-1 cardiomyocytes were incubated with PBS, 0-100 ng/mL IL-39, 200 μM H2O2 or 20 μM Trolox.
IL-39 promoted the production of intracellular reactive oxygen species (ROS) in a concentration dependent manner in HL-1 cardiomyocytes. IL-39 and H2O2 both significantly promoted the production of intracellular ROS, increased the level of intracellular CCL2, stimulated the apoptotic progress of cardiomyocytes, increased the mRNA and protein expression levels of Bax, caspase-3, and p-p38 MAPK, and decreased the mRNA and protein expression levels of Bcl-2. ROS production, CCL2 level, cardiomyocyte apoptosis, and expression of Bax, caspase-3, and p-p38 MAPK were significantly amplified by the administration of IL-39 combined with H2O2, and these processes were significantly alleviated by an antioxidant Trolox.
This study was novel in revealing that IL-39 promoted apoptosis by stimulating the phosphorylation of p38 MAPK in mouse HL-1 cardiomyocytes.
细胞因子白细胞介素（IL）-39是IL-12家族的一个新成员。我们之前的研究发现，急性心肌梗死患者血清中IL-39水平显著升高。然而，IL-39在心肌细胞凋亡中的作用仍不清楚。
在本研究中，将培养的小鼠HL-1心肌细胞与PBS、0-100 ng/mL IL-39、200 μM H2O2或20 μM曲洛秦一起孵育。
IL-39以浓度依赖的方式促进HL-1心肌细胞内活性氧（ROS）的产生。IL-39和H2O2均显著促进细胞内ROS的产生，增加细胞内CCL2水平，刺激心肌细胞的凋亡进程，增加Bax、caspase-3和p-p38 MAPK的mRNA和蛋白表达水平，并降低Bcl-2的mRNA和蛋白表达水平。IL-39与H2O2联合使用可显著放大ROS产生、CCL2水平、心肌细胞凋亡以及Bax、caspase-3和p-p38 MAPK的表达，而抗氧化剂曲洛秦可显著减轻这些过程。
本研究首次揭示IL-39通过刺激小鼠HL-1心肌细胞中p38 MAPK的磷酸化促进细胞凋亡。
