Liu Menglin, Wang Zhen, Zhang Jishou, Ye Di, Wang Menglong, Xu Yao, Zhao Mengmeng, Feng Yongqi, Lu Xiyi, Pan Heng, Pan Wei, Wei Cheng, Tian Dan, Li Wenqiang, Lyu Jingjun, Ye Jing, Wan Jun
Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Front Cardiovasc Med. 2022 Sep 16;9:950029. doi: 10.3389/fcvm.2022.950029. eCollection 2022.
Cardiac dysfunction is one of the most common complications of sepsis and is associated with the adverse outcomes and high mortality of sepsis patients. IL-12p40, the common subunit of IL-12 and IL-23, has been shown to be involved in a variety of inflammation-related diseases, such as psoriasis and inflammatory bowel disease. However, the role of IL-12p40 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains obscure. This study aimed to explore the role of IL-12p40 in LPS-induced cardiac dysfunction and its potential mechanisms.
In this study, mice were treated with LPS and the cardiac expression of IL-12p40 was determined. Then, IL-12p40 mice were used to detect the role and mechanisms of IL-12p40 in LPS-induced cardiac injury. In addition, monocytes were adoptively transferred to IL-12p40 mice to explore their effects on LPS-induced cardiac dysfunction.
The results showed that cardiac IL-12p40 expression was significantly increased after treated with LPS. In addition, IL-12p40 deletion significantly aggravated LPS-induced cardiac dysfunction, evidenced by the increased serum levels of cardiomyocyte injury markers and heart injury scores, as well as by the deteriorated cardiac function. Moreover, IL-12p40 deletion increased LPS-induced monocyte accumulation and cardiac expression of inflammatory cytokines, as well as enhanced the activation of the NF-κB and MAPK pathways. Furthermore, adoptive transfer WT mouse monocytes to IL-12p40 mice alleviated LPS-induced cardiac dysfunction and decreased the phosphorylation of p65.
IL-12p40 deletion significantly aggravated LPS-induced cardiac injury and cardiac dysfunction in mice by regulating the NF-κB and MAPK signaling pathways, and this process was related to monocytes. Therefore, IL-12p40 show a protective role in SIC, and IL-12p40 deficiency or anti-IL-12p40 monoclonal antibodies may be detrimental to patients with SIC.
心脏功能障碍是脓毒症最常见的并发症之一，与脓毒症患者的不良预后和高死亡率相关。白细胞介素12 p40（IL - 12p40）是IL - 12和IL - 23的共同亚基，已被证明参与多种炎症相关疾病，如银屑病和炎症性肠病。然而，IL - 12p40在脂多糖（LPS）诱导的心脏功能障碍中的作用仍不清楚。本研究旨在探讨IL - 12p40在LPS诱导的心脏功能障碍中的作用及其潜在机制。
在本研究中，用LPS处理小鼠并测定心脏中IL - 12p40的表达。然后，使用IL - 12p40基因敲除小鼠检测IL - 12p40在LPS诱导的心脏损伤中的作用和机制。此外，将单核细胞过继转移至IL - 12p40基因敲除小鼠以探讨其对LPS诱导的心脏功能障碍的影响。
结果显示，LPS处理后心脏IL - 12p40表达显著增加。此外，IL - 12p40基因敲除显著加重LPS诱导的心脏功能障碍，表现为心肌损伤标志物血清水平升高、心脏损伤评分增加以及心脏功能恶化。此外，IL - 12p40基因敲除增加了LPS诱导的单核细胞积聚和心脏炎症细胞因子的表达，以及增强了核因子κB（NF - κB）和丝裂原活化蛋白激酶（MAPK）信号通路的激活。此外，将野生型（WT）小鼠单核细胞过继转移至IL - 12p40基因敲除小鼠可减轻LPS诱导的心脏功能障碍并降低p65的磷酸化水平。
IL - 12p40基因敲除通过调节NF - κB和MAPK信号通路显著加重LPS诱导的小鼠心脏损伤和心脏功能障碍，且该过程与单核细胞有关。因此，IL - 12p40在脓毒症诱导的心脏功能障碍中发挥保护作用，IL - 12p40缺乏或抗IL - 12p40单克隆抗体可能对脓毒症诱导的心脏功能障碍患者有害。
