Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice

A20 is a cytoplasmic zinc finger protein that inhibits nuclear factor kappa B (NF-kappa B) activity and tumor necrosis factor (TNF)-mediated programmed cell death (PCD). TNF dramatically increases A20 messenger RNA expression in all tissues. Mice deficient far A20 develop severe inflammation and cachexia, are hypersensitive to both Lipopolysaccharide and TNF, and die prematurely. A20-deficient cells fail to terminate TNF-induced NF-kappa B responses. These cells are also more susceptible than control cells to undergo TNF-mediated PCD. Thus, AZO is critical for limiting inflammation by terminating TNF-induced NF-kappa B responses in vivo.