Identification and validation of metformin protects against PM2.5-induced macrophages cytotoxicity by targeting toll like receptor pathway.

Identification and validation of metformin protects against PM2.5-induced macrophages cytotoxicity by targeting toll like receptor pathway. Chemosphere. 2020 Jul;251:126526 Authors: Shi Y, Batibawa JW, Maiga M, Sun B, Li Y, Duan J, Sun Z Abstract Fine particle matter (PM2.5) has been extensively reported to contribute to the pathogenesis of pulmonary diseases. Recently, metformin has been reported to attenuate PM2.5 associated respiratory and cardiovascular injury, but the underling mechanism has not been discovered. Here, we performed comprehensively bioinformatics analysis and fully validation experiment to investigate the protection role of metformin and underling mechanism with RNAseq profile in GEO database. A combination of various bioinformatics tools including edgeR, principal component analysis (PCA), K-Means clustering, Gene Set Enrichment Analysis (GSEA), GO and KEGG enrichment were performed to identify the TLRs/MyD88/NF-κB axis functional as the key signaling transduction during PM2.5 associated toxicity. PM2.5 activated TLRs/MyD88/NF-κB pathway and resulted in significantly generation of IL-6, TNF-α, mitochondrial damage, decreasing of cell viability and increased LDH activity in RAW264.7 cells. Metformin significantly attenuated the production of IL-6, mitochondrial damage, cell viability and LDH activity by limiting TLRs/MyD88/NF-κB pathway. The siRNA against AMPKα2 or negative control were transfected to RAW264...
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research