The role of IFN-γ in regulating Nfkbiz expression in epidermal keratinocytes

• Published in: Biomedical Research Vol. 36; no. 2; pp. 103 - 107
• Main Authors: ISHIGURO-OONUMA, Toshina, OCHIAI, Kazuhiko, HASHIZUME, Kazuyoshi, MORIMATSU, Masami
• Format: Journal Article
• Language: English
• Published: Japan Biomedical Research Press 2015
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Cells, Cultured; Epidermis - cytology; Gene Expression Regulation - immunology; Interferon-gamma - physiology; Keratinocytes - immunology; Keratinocytes - metabolism; Mice, Inbred C57BL; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Promoter Regions, Genetic
• ISSN: 0388-6107; 1880-313X
• DOI: 10.2220/biomedres.36.103

Nfkbiz is an inhibitor of nuclear factor κB (IκB) protein localized to the nucleus. We previously found that Nfkbiz gene-disrupted mice showed atopic dermatitis-like lesion, implying the important role of Nfkbiz in skin homeostasis. The purpose of this study was to examine the effect of interferon (IFN)-γ on Nfkbiz expression in keratinocytes. IFN-γ induced Nfkbiz expression at a comparable level to IL-1. Promoter analysis revealed that interferon-stimulated response element (ISRE) located in the Nfkbiz promoter region is important for responding to the stimulation. Interestingly, IFN-γ and IL-1 displayed synergism in terms of inducing Nfkbiz expression. By using selective inhibitors, we found that Janus activated kinase (JAK) 1 and nuclear factor (NF)-κB are important for Nfkbiz expression after IFN-γ stimulation and for synergism between IFN-γ and IL-1. These findings indicate a possible important role of Nfkbiz in modulating the progression of inflammatory diseases in which IFN-γ and IL-1 are abundant.