Macrophage-preferable delivery of the leucine-rich repeat domain of NLRX1 ameliorates lethal sepsis by regulating NF-κB and inflammasome signaling activation

摘要: Abstract Sepsis is an acute systemic inflammatory disease triggered by bacterial infection leading organ dysfunctions that macrophages are responsible for major triggering of inflammation. Treatment options limited to antibiotics and drugs manage the symptoms sepsis, but there currently no molecular-targeted therapies. Here, we identified a novel macrophage-preferable delivery peptide, C10, which conjugated truncated domains NLRX1 (leucine-rich repeat region (LRR), nucleotide binding domain (NBD)) obtain C10-LRR C10-NBD. Leucine rich amino acid C10 enables macrophage preferable moieties efficiently deliver cargo protein into in vitro vivo . not C10-NBD significantly improved survival LPS-mediated lethal endotoxemia sepsis model. inhibited IL-6 production peritoneal via prevention IκB degradation p65 phosphorylation. In addition, negatively regulated IL-1β preventing caspase-1 activation with sustained mitochondrial MAVS level. Finally, co-treatment anti-TNFα antibody had synergistic effect LPS-induced Collectively, these findings indicate could be effective therapeutic agent treat inflammation regulating both NF-κB inflammasome signaling activation.