IκB-ζ, a new anti-inflammatory nuclear protein induced by lipopolysaccharide, is a negative regulator for nuclear factor-κB

Abstract

Activation of nuclear factor-κ B (NF-κ B), a prominent cellular response to bacterial endotoxin or other microbial products, must be strictly regulated because excessive activation leads to overproduction of cytotoxic cytokines that culminates in septic shock. During screening for genes up-regulated upon inflammation, we identified a new member of the IκB family proteins with the ankyrin-repeats. This protein, designated Iκ B-ζ , is hardly detectable in resting cells, but is strongly induced upon stimulation by lipopolysaccharide, which stimulates cells through the Toll-like receptor 4. Interleukin-1β stimulation also results in the strong induction of IκB-ζ, but tumor necrosis factor-α does not. In contrast to IκB-α or Iκ B-β , IκB-ζ localizes in the nucleus, where it inhibits NF-κB activity. NF-κ B activity is essential for the induction of IκB-ζ, but is not sufficient. Thus, this protein is a new anti-inflammatory protein, which is specifically induced upon inflammation to regulate NF-κB activity.