Nfkbiz regulates the proliferation and differentiation of keratinocytes

Nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-kappa B) inhibitor zeta (Nfkbiz) is a nuclear inhibitor of NF-kappa B (I kappa B) protein that is also termed as molecule possessing ankyrin repeats induced by lipopolysaccharide, interleukin-1-inducible nuclear ankyrin repeat protein, or I kappa B zeta; We found previously that disrupting the Nfkbiz gene resulted in atopic dermatitis-like lesions in mice, suggesting an important role for Nfkbiz in the skin. In this study, we examined the cellular function of Nfkbiz in keratinocytes. Immunohistochemical analyses for Ki-67 revealed that Nfkbiz(-/-) keratinocytes were hypoproliferative. In skin from Nfkbiz(-/-) mice, the expression of the keratinocyte differentiation markers K10 and filaggrin were reduced, although that of K14 was unchanged. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay revealed that the frequency of apoptosis was comparable between control and Nfkbiz(-/-) keratinocytes. Interestingly, the subcellular localization of the NF-kappa B subunits and the transcriptional activity of NF-kappa B were not changed in Nfkbiz(-/-) keratinocytes. These findings indicate a novel possible role of Nfkbiz in controlling the proliferation and differentiation of epidermal keratinocytes through NF-kappa B-independent mechanisms.