CHTOP Promotes Microglia-Mediated Inflammation by Regulating Cell Metabolism and Inflammatory Gene Expression

During the initiation of the inflammatory response of microglia, the expression of many inflammation- and cell metabolism -related genes alters. However, how the transcription of inflammation- and metabolism -related genes are coordinately regulated during inflammation initiation is poorly understood. In this study, we found that LPS stimulation induced the expression of the chromatin target of PRMT1 (protein arginine methyltransferase 1) (CHTOP) in microglia. Knocking down CHTOP in microglia decreased proinflammatory cytokine expression. In addition, CHTOP knockdown altered cell metabolism, as both the upregulated genes were enriched in cell metabolism -related pathways and the metabolites profile was greatly altered based on untargeted metabolomics analysis. Mechanistically, CHTOP could directly bind the regulatory elements of inflammation and cell metabolism -related genes to regulate their transcription. In addition, knocking down CHTOP increased neuronal viability in vitro and alleviated microgliamediated neuroinflammation in a systemic LPS treatment mouse model. Collectively, these data revealed CHTOP as a novel regulator to promote microglia-mediated neuroinflammation by coordinately regulating the transcription of inflammation and cell metabolism -related genes. The Journal of Immunology, 2024, 212: 677-688.