IL-4 and IL-13 negatively regulate TNF-β- and IFN-γ-induced β-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3

Cristina Albanesi, Heather R. Fairchild, Stefania Madonna, Claudia Scarponi, Ornella De Pità, D. Y M Leung, Michael D. Howell

Research output: Contribution to journalArticle

Abstract

Human β-defensins (HBDs) are a major class of antimicrobial peptides that play an important role in the innate immune response, however, the induction and regulation of these antimicrobial peptides is not well understood. We demonstrate here that stimulation of keratinocytes with TNF-α/IFN- γ induces HBD-2 and HBD-3 by activating STAT-1 and NF-κB signaling. We further demonstrate that IL-4 and IL-13 activate STAT-6 and induce the suppressors of cytokine signaling (SOCS)-1 and -3. This interferes with STAT-1 and NF-κB signaling, thereby inhibiting TNF-α/IFN-γ-mediated induction of HBD-2 and HBD-3. These data suggest that targeting the STAT-1-signaling pathway or suppressor of cytokine signaling expression enhances β-defensin expression and represents a new therapeutic strategy for reduction of infection in human diseases associated with β-defensin deficiency.

Original languageEnglish
Pages (from-to)984-992
Number of pages9
JournalJournal of Immunology
Volume179
Issue number2
Publication statusPublished - Jul 15 2007

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Defensins
Interleukin-13
Interleukin-4
Cytokines
Peptides
Keratinocytes
Innate Immunity
Infection
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

IL-4 and IL-13 negatively regulate TNF-β- and IFN-γ-induced β-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3. / Albanesi, Cristina; Fairchild, Heather R.; Madonna, Stefania; Scarponi, Claudia; De Pità, Ornella; Leung, D. Y M; Howell, Michael D.

In: Journal of Immunology, Vol. 179, No. 2, 15.07.2007, p. 984-992.

Research output: Contribution to journalArticle

Albanesi, Cristina ; Fairchild, Heather R. ; Madonna, Stefania ; Scarponi, Claudia ; De Pità, Ornella ; Leung, D. Y M ; Howell, Michael D. / IL-4 and IL-13 negatively regulate TNF-β- and IFN-γ-induced β-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3. In: Journal of Immunology. 2007 ; Vol. 179, No. 2. pp. 984-992.
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AU - Madonna, Stefania

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AU - De Pità, Ornella

AU - Leung, D. Y M

AU - Howell, Michael D.

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