Bcl-3 acts as an innate immune modulator by controlling antimicrobial responses in keratinocytes

Amanda S. Büchau, Daniel T. MacLeod, Shin Morizane, Paul F. Kotol, Tissa Hata, Richard L. Gallo

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2148-2155
Number of pages8
JournalJournal of Investigative Dermatology
Volume129
Issue number9
DOIs
Publication statusPublished - Sep 2009
Externally publishedYes

Fingerprint

B-Cell Leukemia
Keratinocytes
Interleukin-4
Modulators
Cytokines
Interleukin-13
Cholecalciferol
Transcription
Chemokines
Gene expression
Small Interfering RNA
Innate Immunity
Skin
Cells
Peptides
Atopic Dermatitis
Gene Expression
CAP18 lipopolysaccharide-binding protein
cathelicidin antimicrobial peptide

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Bcl-3 acts as an innate immune modulator by controlling antimicrobial responses in keratinocytes. / Büchau, Amanda S.; MacLeod, Daniel T.; Morizane, Shin; Kotol, Paul F.; Hata, Tissa; Gallo, Richard L.

In: Journal of Investigative Dermatology, Vol. 129, No. 9, 09.2009, p. 2148-2155.

Research output: Contribution to journalArticle

Büchau, Amanda S. ; MacLeod, Daniel T. ; Morizane, Shin ; Kotol, Paul F. ; Hata, Tissa ; Gallo, Richard L. / Bcl-3 acts as an innate immune modulator by controlling antimicrobial responses in keratinocytes. In: Journal of Investigative Dermatology. 2009 ; Vol. 129, No. 9. pp. 2148-2155.
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