The soluble form of the migration inhibitory factor receptor cluster of differentiation 74 (sCD74) has previously been shown to be elevated during the development of acute lung injury (ALI) in mice. However, the biological role of increased sCD74 in ALI remans poorly understood. Synthesized recombinant sCD74 protein was administered to mice intratracheally. Pro-inflammatory genes in lung tissue and the inflammatory factors in bronchoalveolar lavage fluid (BALF) were analyzed using RT-PCR and ELISA, respectively. Additionally, RAW264.7, A549, and human umbilical vein endothelial cells (HUVEC) were treated with sCD74, and the resulting pro-inflammatory factor protein and gene expression levels were analyzed in the supernatants and cell lysates. Meanwhile, the level of nuclear factor (NF)-κB components in cell lysates after stimulating macrophages with sCD74 was also assessed. After administration of 0.5 mg/kg body weight sCD74 to mice, the expression of Tnfa, Mip2, and Il6 increased in lung tissues after 2 h by 2.1-, 3.4-, and 2.8-fold, respectively. Moreover, the BALF concentrations of TNF-α and MIP-2 reached maximal levels of 560 and 107 pg/mL at 8 h compared to those in the saline group, respectively. Similarly, TNFA, MIP2, and IL6 expression increased by 4.0-, 11.8-, and 2.6-fold, respectively, 2 h after stimulating macrophages with 1000 ng/mL sCD74. The levels of phospho-IκB and phospho-p65 were also significantly increased in the cytoplasm and nucleus of macrophages following sCD74 stimulation. Taken together, these results suggest that sCD74 is a critical cellular factor involved in the lung acute inflammatory response through nuclear factor-κB signaling.

先前已显示迁移抑制因子受体分化簇 74 (sCD74) 的可溶性形式在小鼠急性肺损伤 (ALI) 的发展过程中升高。然而，sCD74 在 ALI 中增加的生物学作用仍然知之甚少。将合成的重组 sCD74 蛋白气管内施用于小鼠。分别使用RT-PCR和ELISA分析肺组织中的促炎基因和支气管肺泡灌洗液（BALF）中的炎性因子。此外，RAW264.7、A549 和人脐静脉内皮细胞 (HUVEC) 用 sCD74 处理，并在上清液和细胞裂解物中分析了产生的促炎因子蛋白和基因表达水平。同时，还评估了用 sCD74 刺激巨噬细胞后细胞裂解物中核因子 (NF)-κB 成分的水平。给小鼠施用 0.5 mg/kg 体重的 sCD74 后，2 小时后，肺组织中的Tnfa、Mip2和Il6 分别增加了 2.1、3.4 和 2.8 倍。此外，与生理盐水组相比，TNF-α 和 MIP-2 的 BALF 浓度在 8 小时时分别达到最高水平 560 和 107 pg/mL。类似地，在用 1000 ng/mL sCD74 刺激巨噬细胞 2 小时后，TNFA 、MIP2和IL6 的表达分别增加了 4.0、11.8 和 2.6 倍。在 sCD74 刺激后，巨噬细胞的细胞质和细胞核中磷酸-IκB 和磷酸-p65 的水平也显着增加。总之，这些结果表明 sCD74 是通过核因子-κB 信号传导参与肺急性炎症反应的关键细胞因子。