Cargando…
Requirements for Two Proximal NF-κB Binding Sites and IκB-ζ in IL-17A-induced Human β-Defensin 2 Expression by Conducting Airway Epithelium
Among a panel of 21 cytokines (IL-1α, -1β, -2–13, and -15–18; interferon-γ; granulocyte-macrophage colony-stimulating factor; and tumor necrosis factor α), we have recently observed that IL-17A is the most potent inducer for human β-defensin 2 (hBD-2) in conducting airway epithelial cells (Kao, C. Y...
Autores principales: | , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2008
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2397472/ https://www.ncbi.nlm.nih.gov/pubmed/18362142 http://dx.doi.org/10.1074/jbc.M708289200 |
_version_ | 1782155628245942272 |
---|---|
author | Kao, Cheng-Yuan Kim, Christy Huang, Fei Wu, Reen |
author_facet | Kao, Cheng-Yuan Kim, Christy Huang, Fei Wu, Reen |
author_sort | Kao, Cheng-Yuan |
collection | PubMed |
description | Among a panel of 21 cytokines (IL-1α, -1β, -2–13, and -15–18; interferon-γ; granulocyte-macrophage colony-stimulating factor; and tumor necrosis factor α), we have recently observed that IL-17A is the most potent inducer for human β-defensin 2 (hBD-2) in conducting airway epithelial cells (Kao, C. Y., Chen, Y., Thai, P., Wachi, S., Huang, F., Kim, C., Harper, R. W., and Wu, R. (2004) J. Immunol. 173, 3482–3491). The molecular basis of this regulation is not known. In this study, we demonstrated a coordinated degradation of inhibitory κB(IκB)-α followed by a nuclear translocation of p50 and p65 NF-κB subunits and their binding to NF-κB sites of hBD-2 promoter region. With site-directed mutagenesis, we demonstrated the requirement of two proximal NF-κB binding sites (pκB1, -205 to -186; pκB2, -596 to -572) but not the distal site (dκB, -2193 to -2182) in supporting IL-17A-induced hBD-2 promoter activity. These results are consistent with the data of the chromatin immunoprecipitation assay, which showed enhanced p50 binding to these pκB sites but not the dκB site in cells after IL-17A treatment. We also found that the NF-κB binding cofactor, IκB-ζ, was up-regulated by IL-17A, and the knockdown of IκB-ζ significantly diminished the IL-17A-induced hBD-2 expression. This is the first demonstration of the involvement of two proximal NF-κB sites and IκB-ζ in the regulation of hBD-2 by IL-17A, two important genes responsible for host defense. |
format | Text |
id | pubmed-2397472 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-23974722008-12-18 Requirements for Two Proximal NF-κB Binding Sites and IκB-ζ in IL-17A-induced Human β-Defensin 2 Expression by Conducting Airway Epithelium Kao, Cheng-Yuan Kim, Christy Huang, Fei Wu, Reen J Biol Chem Transcription, Chromatin, and Epigenetics Among a panel of 21 cytokines (IL-1α, -1β, -2–13, and -15–18; interferon-γ; granulocyte-macrophage colony-stimulating factor; and tumor necrosis factor α), we have recently observed that IL-17A is the most potent inducer for human β-defensin 2 (hBD-2) in conducting airway epithelial cells (Kao, C. Y., Chen, Y., Thai, P., Wachi, S., Huang, F., Kim, C., Harper, R. W., and Wu, R. (2004) J. Immunol. 173, 3482–3491). The molecular basis of this regulation is not known. In this study, we demonstrated a coordinated degradation of inhibitory κB(IκB)-α followed by a nuclear translocation of p50 and p65 NF-κB subunits and their binding to NF-κB sites of hBD-2 promoter region. With site-directed mutagenesis, we demonstrated the requirement of two proximal NF-κB binding sites (pκB1, -205 to -186; pκB2, -596 to -572) but not the distal site (dκB, -2193 to -2182) in supporting IL-17A-induced hBD-2 promoter activity. These results are consistent with the data of the chromatin immunoprecipitation assay, which showed enhanced p50 binding to these pκB sites but not the dκB site in cells after IL-17A treatment. We also found that the NF-κB binding cofactor, IκB-ζ, was up-regulated by IL-17A, and the knockdown of IκB-ζ significantly diminished the IL-17A-induced hBD-2 expression. This is the first demonstration of the involvement of two proximal NF-κB sites and IκB-ζ in the regulation of hBD-2 by IL-17A, two important genes responsible for host defense. American Society for Biochemistry and Molecular Biology 2008-05-30 /pmc/articles/PMC2397472/ /pubmed/18362142 http://dx.doi.org/10.1074/jbc.M708289200 Text en Copyright © 2008, The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Transcription, Chromatin, and Epigenetics Kao, Cheng-Yuan Kim, Christy Huang, Fei Wu, Reen Requirements for Two Proximal NF-κB Binding Sites and IκB-ζ in IL-17A-induced Human β-Defensin 2 Expression by Conducting Airway Epithelium |
title | Requirements for Two Proximal NF-κB Binding Sites and IκB-ζ in IL-17A-induced Human β-Defensin 2 Expression by Conducting Airway Epithelium |
title_full | Requirements for Two Proximal NF-κB Binding Sites and IκB-ζ in IL-17A-induced Human β-Defensin 2 Expression by Conducting Airway Epithelium |
title_fullStr | Requirements for Two Proximal NF-κB Binding Sites and IκB-ζ in IL-17A-induced Human β-Defensin 2 Expression by Conducting Airway Epithelium |
title_full_unstemmed | Requirements for Two Proximal NF-κB Binding Sites and IκB-ζ in IL-17A-induced Human β-Defensin 2 Expression by Conducting Airway Epithelium |
title_short | Requirements for Two Proximal NF-κB Binding Sites and IκB-ζ in IL-17A-induced Human β-Defensin 2 Expression by Conducting Airway Epithelium |
title_sort | requirements for two proximal nf-κb binding sites and iκb-ζ in il-17a-induced human β-defensin 2 expression by conducting airway epithelium |
topic | Transcription, Chromatin, and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2397472/ https://www.ncbi.nlm.nih.gov/pubmed/18362142 http://dx.doi.org/10.1074/jbc.M708289200 |
work_keys_str_mv | AT kaochengyuan requirementsfortwoproximalnfkbbindingsitesandikbzinil17ainducedhumanbdefensin2expressionbyconductingairwayepithelium AT kimchristy requirementsfortwoproximalnfkbbindingsitesandikbzinil17ainducedhumanbdefensin2expressionbyconductingairwayepithelium AT huangfei requirementsfortwoproximalnfkbbindingsitesandikbzinil17ainducedhumanbdefensin2expressionbyconductingairwayepithelium AT wureen requirementsfortwoproximalnfkbbindingsitesandikbzinil17ainducedhumanbdefensin2expressionbyconductingairwayepithelium |