IκBβ is a member of the IκB family of proteins, which play a crucial role in regulating the activity of NF-κB transcription factors. IκBβ, like IκBα, can sequester NF-κB dimers in the cytoplasm, preventing their translocation to the nucleus and thus inhibiting the expression of NF-κB-dependent genes. Upon stimulation by lipopolysaccharide (LPS), IκBβ is slowly degraded and re-synthesized as a hypophosphorylated form that can enter the nucleus. This nuclear IκBβ can bind to NF-κB dimers such as p65:c-Rel, stabilizing them and promoting the expression of specific pro-inflammatory genes like TNF-α. Interestingly, IκBβ−/− mice show a dramatic reduction in TNF-α production in response to LPS and are resistant to LPS-induced septic shock and collagen-induced arthritis. This suggests that IκBβ not only acts as an inhibitor of NF-κB but also as a positive regulator of certain NF-κB-dependent genes, highlighting its dual role in the inflammatory response.
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