NF-κB RelA Is Required for Hepatoprotection during Pneumonia and Sepsis

Abstract

) mice during pneumonia. The absence of RelA resulted in hepatotoxicity across several models of pneumonia, sepsis, and NKT cell activation. Injury was associated with increased levels of activated caspase-3 and -8 and substantial alteration of the hepatic transcriptome. Hepatotoxicity in the absence of RelA could be reversed by neutralization of tumor necrosis factor alpha (TNF-α). These results indicate the requirement of RelA-dependent inducible hepatoprotection during pneumonia and sepsis. Further, the results demonstrate that RelA-dependent gene programs are critical for maintaining liver homeostasis against TNF-α-driven immunotoxicity.