Silencing of lncRNA Gm26917 Attenuates Alveolar Macrophage-mediated Inflammatory Response in LPS-induced Acute Lung Injury Via Inhibiting NKRF Ubiquitination

The inflammatory response mediated by alveolar macrophages plays a crucial role in the development of acute lung injury. Numerous studies have reported that lncRNAs are highly expressed in acute lung injury in mouse models and cell lines, and acute lung injury (ALI) can be effectively alleviated by targeting these lncRNAs. The aim of this study was to explore the mechanism by LncRNA Gm26917 regulates the inflammatory response in alveolar macrophages during acute lung injury mouse model. We initially observed a significant upregulation of Gm26917 expression in both ALI conditions and in MH-S cells treated with LPS. Furthermore, the silencing of Gm26917 via lentivirus-mediated methods conferred protection against LPS-induced ALI. Additionally, siRNA-mediated knockdown of Gm26917 attenuated LPS-induced inflammatory responses and modulated the function of alveolar macrophages. Subsequent mechanistic studies revealed that Gm26917 interacts with NKRF, and its knockdown suppressed NKRF ubiquitination, thereby enhancing NKRF binding to p50 and subsequently inhibiting the NF-kappa B signaling pathway. In conclusion, our findings demonstrate that silencing Gm26917 can mitigate LPS-induced ALI by modulating the NF-kappa B signaling pathway in alveolar macrophages through interactions with NKRF.