IL-17A enhances vitamin D3-induced expression of cathelicidin antimicrobial peptide in human keratinocytes

Mark Peric, Sarah Koglin, Song Min Kim, Shin Morizane, Robert Besch, Jörg C. Prinz, Thomas Ruzicka, Richard L. Gallo, Jürgen Schauber

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135 Citations (Scopus)

Abstract

Cathelicidin is strongly expressed in lesional skin in psoriasis and may play an important role as both an antimicrobial peptide and as an autoinflammatory mediator in this chronic skin disease. The mechanism of increased cathelicidin in psoriatic keratinocytes is not known, but recent observations have found that psoriasis has abundant Th17 cells that produce IL-17A and IL-22. We found that human keratinocytes stimulated with supernatants from T cells isolated from lesional psoriatic skin increased expression of cathelicidin when stimulated in the presence of 1,25-dihydroxyvitamin D 3 (1,25D3). This increase was signaled through the IL-17RA. In vitro, IL-17A, but not IL-22, enhanced cathelicidin mRNA and peptide expression in keratinocytes dependent on the presence of 1,25D3. At the same time, coincubation with 1,25D3 blocked induction of human β-defensin 2 (HBD2), IL-6, and IL-8, which are other target genes of IL-17A. Act1, an adaptor associated with IL-17RA and essential for IL-17A signaling, mediated cathelicidin induction, as its suppression by small interfering RNA inhibited HBD2 and cathelicidin. Both, 1,25D3 and IL-17A signaled cathelicidin induction through MEK-ERK. These results suggest that increased IL-17A in psoriatic skin increases cathelicidin through a vitamin D3-, Act1-, and MEK-ERK-dependent mechanism. Therapy targeting this cathelicidin-regulating system might be beneficial in patients suffering from psoriasis.

Original languageEnglish
Pages (from-to)8504-8512
Number of pages9
JournalJournal of Immunology
Volume181
Issue number12
DOIs
Publication statusPublished - Dec 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Peric, M., Koglin, S., Kim, S. M., Morizane, S., Besch, R., Prinz, J. C., Ruzicka, T., Gallo, R. L., & Schauber, J. (2008). IL-17A enhances vitamin D3-induced expression of cathelicidin antimicrobial peptide in human keratinocytes. Journal of Immunology, 181(12), 8504-8512. https://doi.org/10.4049/jimmunol.181.12.8504