TNF and acute kidney injury: In experimental AKI models, ischemia–reperfusion injury (IRI) induces rapid activation of NF-κB in tubular epithelial cells and infiltrating immune cells, promoting expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β [70] demonstrated that inhibition of cullin-RING E3 ligases by MLN4924, a small molecule inhibitor of the NEDD8-activating enzyme, attenuated NF-κB activation and reduced inflammation in a mouse model of IRI-induced AKI.