{Reference Type}: Journal Article
{Title}: Azithromycin regulates Mettl3-mediated NF-κB pathway to enhance M2 polarization of RAW264.7 macrophages and attenuate LPS-triggered cytotoxicity of MLE-12 alveolar cells.
{Author}: Xu S;Xing J;Zheng L;Su H;Zou Y;Niu Y;Di H;
{Journal}: Int Immunopharmacol
{Volume}: 137
{Issue}: 0
{Year}: 2024 Jun 14
{Factor}: 5.714
{DOI}: 10.1016/j.intimp.2024.112426
{Abstract}: <B>BACKGROUND: </B>Azithromycin (AZM) has been proposed as a potential therapeutic drug in acute pulmonary injury due to its immunomodulatory and anti-inflammatory properties. However, its therapeutic mechanism remains not fully understood.<BR><B>METHODS: </B>LPS was used to stimulate MLE-12 cells and RAW264.7 macrophages. Analyses of viability and apoptosis were performed by CCK-8 assay and flow cytometry, respectively. Protein analysis was performed by immunoblotting, and mRNA expression was tested by quantitative PCR. The secretion levels of TNF-α and IL-6 were detected by ELISA. MDA, GSH, ROS and Fe2+ contents were analyzed using assay kits.<BR><B>RESULTS: </B>Administration of AZM or depletion of methyltransferase-like 3 (Mettl3) could attenuate LPS-triggered apoptosis, inflammation and ferroptosis in MLE-12 alveolar cells, as well as enhance M2 polarization of LPS-stimulated RAW264.7 macrophages. In LPS-exposed MLE-12 and RAW264.7 cells, AZM reduced Mettl3 protein expression and inactivated the NF-κB signaling through downregulation of Mettl3. Furthermore, Mettl3 restoration abated AZM-mediated anti-apoptosis, anti-inflammation and anti-ferroptosis effects in LPS-exposed MLE-12 cells and reversed AZM-mediated M2 polarization enhancement of LPS-exposed RAW264.7 macrophages.<BR><B>CONCLUSIONS: </B>Our study indicates that AZM can promote M2 polarization of LPS-exposed RAW264.7 macrophages and attenuate LPS-triggered injury of MLE-12 alveolar cells by inactivating the Mettl3-mediated NF-κB pathway.