Department of Laboratory Medicine, Qishan Hospital, Yantai, Shandong, China.
Department of Microbiology Laboratory, Huangdao District Center for Disease Control and Prevention, Qingdao, Shandong, China.
Autoimmunity. 2022 Dec;55(8):587-596. doi: 10.1080/08916934.2022.2114465. Epub 2022 Aug 21.
Acute lung injury (ALI) is considered as a severe respiratory disease with aggravated inflammatory responses. Krüppel-like factor 9 (), a member of KLF family, has been reported to be involved in inflammatory disorders. However, the effect of in ALI has not been elucidated. Here the present study was to clarify the role of and its mechanism in ALI. The ALI model was established with lipopolysaccharide (LPS)-treated RAW264.7 cells. Mice were injected with LPS to conduct an ALI model. The expression of and gasdermin D () was examined using quantitative reverse transcription-PCR, haematoxylin-eosin/immunohistochemistry staining and western blot assays. Enzyme-linked immunosorbent assay was employed to detect the levels of inflammatory cytokines. JASPAR database was used to predict the recognition motif of , and the relationship between and was determined by luciferase reporter assay and chromatin immunoprecipitation analysis. The number of neutrophils in bronchoalveolar lavage fluid as well as the wet/dry weight ratio was caculated. The results showed that The expression of in lung was significantly increased in LPS-stimulated mice. Moreover, knockout relieved the lung injury in ALI mice. is one of targets genes of the transcription factor . knockout induced a decreased expression of in LPS-treated mice. Furthermore, in RAW264.7 cells after LPS administration, knockdown reduced the levels of inflammatory factors and suppressed the expression of . In summarise, these findings exhibited that knockout could mitigate the lung injury and inflammatory responses in ALI mice by directly regulating .
急性肺损伤（ALI）被认为是一种伴有加重炎症反应的严重呼吸系统疾病。Krüppel 样因子 9（），是 KLF 家族的一员，据报道与炎症性疾病有关。然而，在 ALI 中 的作用尚未阐明。本研究旨在阐明在 ALI 中 的作用及其机制。采用脂多糖（LPS）处理的 RAW264.7 细胞建立 ALI 模型。用 LPS 注射小鼠建立 ALI 模型。采用定量逆转录-PCR、苏木精-伊红/免疫组织化学染色和 Western blot 检测 及气 孔 蛋白 D（）的表达。酶联免疫吸附试验检测炎症细胞因子水平。JASPAR 数据库用于预测 的识别基序，并通过荧光素酶报告基因检测和染色质免疫沉淀分析确定 与 的关系。计算支气管肺泡灌洗液中中性粒细胞的数量和湿/干重比。结果表明，LPS 刺激的小鼠肺中 的表达明显增加。此外， 敲除减轻了 ALI 小鼠的肺损伤。 是转录因子 的靶基因之一。在 LPS 处理的小鼠中， 敲除导致 的表达降低。此外，在 LPS 处理的 RAW264.7 细胞中， 敲低降低了炎症因子的水平，并抑制了 的表达。综上所述，这些发现表明， 通过直接调节 ， 敲除可减轻 ALI 小鼠的肺损伤和炎症反应。
