Our insights are anchored in comprehensive RNA-seq analyses on ARDS lungs and LPS-treated CtBP2KD/p300KD/p65KD cells, which emphasized the pivotal role of IL-1β, IL-6, IL-8, IL-15, TNF-α, and IFN-γ in LPS-challenged ARDS and the important role of the CtBP2-p300-NF-κB complex in modulating proinflammatory genes, with minor influence on other CtBP2, p300, and NF-κB target genes. Here, TNF is linked to acute respiratory distress syndrome.