Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2008-5-26
pubmed:abstractText
Among a panel of 21 cytokines (IL-1alpha, -1beta, -2-13, and -15-18; interferon-gamma; granulocyte-macrophage colony-stimulating factor; and tumor necrosis factor alpha), we have recently observed that IL-17A is the most potent inducer for human beta-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 kappaB(IkappaB)-alpha followed by a nuclear translocation of p50 and p65 NF-kappaB subunits and their binding to NF-kappaB sites of hBD-2 promoter region. With site-directed mutagenesis, we demonstrated the requirement of two proximal NF-kappaB binding sites (pkappaB1, -205 to -186; pkappaB2, -596 to -572) but not the distal site (dkappaB, -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 pkappaB sites but not the dkappaB site in cells after IL-17A treatment. We also found that the NF-kappaB binding cofactor, IkappaB-zeta, was up-regulated by IL-17A, and the knockdown of IkappaB-zeta significantly diminished the IL-17A-induced hBD-2 expression. This is the first demonstration of the involvement of two proximal NF-kappaB sites and IkappaB-zeta in the regulation of hBD-2 by IL-17A, two important genes responsible for host defense.
pubmed:grant
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15309-18
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
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