Abstract
Innate immune responses involve the production of antimicrobial peptides (AMPs), chemokines, and cytokines. We report here the identification of B-cell leukemia (Bcl)-3 as a modulator of innate immune signaling in keratinocytes. In this study, it is shown that Bcl-3 is inducible by the Th2 cytokines IL-4 and IL-13 and is overexpressed in lesional skin of atopic dermatitis (AD) patients. Bcl-3 was shown to be important to cutaneous innate immune responses as silencing of Bcl-3 by small-interfering RNA (siRNA) reversed the downregulatory effect of IL-4 on the HBD3 expression. Bcl-3 silencing enhanced vitamin D3 (1,25D3)-induced gene expression of cathelicidin AMP in keratinocytes, suggesting a negative regulatory function on cathelicidin transcription. Furthermore, 1,25D3 suppressed Bcl-3 expression in vitro and in vivo. This study identified Bcl-3 as an important modulator of cutaneous innate immune responses and its possible therapeutic role in AD.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Antimicrobial Cationic Peptides / genetics
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Antimicrobial Cationic Peptides / physiology
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B-Cell Lymphoma 3 Protein
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Cathelicidins
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Cells, Cultured
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Cholecalciferol / analogs & derivatives
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Cholecalciferol / pharmacology
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Dermatitis, Atopic / immunology
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Humans
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Immunity, Innate*
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Interleukin-13 / pharmacology
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Interleukin-4 / pharmacology
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Interleukin-6 / biosynthesis
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Interleukin-8 / biosynthesis
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Keratinocytes / immunology*
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Molecular Sequence Data
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NF-kappa B p50 Subunit / physiology
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Proto-Oncogene Proteins / physiology*
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Transcription Factors / physiology*
Substances
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1,25-dihydroxy-16,23-diene vitamin D3
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Antimicrobial Cationic Peptides
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B-Cell Lymphoma 3 Protein
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BCL3 protein, human
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Interleukin-13
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Interleukin-6
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Interleukin-8
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NF-kappa B p50 Subunit
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Proto-Oncogene Proteins
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Transcription Factors
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Cholecalciferol
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Interleukin-4
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Cathelicidins