Vitamin D analogs differentially control antimicrobial peptide/"alarmin" expression in psoriasis

Mark Peric, Sarah Koglin, Yvonne Dombrowski, Katrin Gross, Eva Bradac, Amanda Büchau, Andreas Steinmeyer, Ulrich Zügel, Thomas Ruzicka, Jürgen Schauber

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)

Abstract

Antimicrobial peptides (AMPs) are strongly expressed in lesional skin in psoriasis and play an important role as proinflammatory "alarmins" in this chronic skin disease. Vitamin D analogs like calcipotriol have antipsoriatic effects and might mediate this effect by changing AMP expression. In this study, keratinocytes in lesional psoriatic plaques showed decreased expression of the AMPs beta-defensin (HBD) 2 and HBD3 after topical treatment with calcipotriol. At the same time, calcipotriol normalized the proinflammatory cytokine milieu and decreased interleukin (IL)-17A, IL-17F and IL-8 transcript abundance in lesional psoriatic skin. In contrast, cathelicidin antimicrobial peptide expression was increased by calcipotriol while psoriasin expression remained unchanged. In cultured human epidermal keratinocytes the effect of different vitamin D analogs on the expression of AMPs was further analyzed. All vitamin D analogs tested blocked IL-17A induced HBD2 expression by increasing IkappaB-alpha protein and inhibition of NF-kappaB signaling. At the same time vitamin D analogs induced cathelicidin through activation of the vitamin D receptor and MEK/ERK signaling. These studies suggest that vitamin D analogs differentially alter AMP expression in lesional psoriatic skin and cultured keratinocytes. Balancing AMP "alarmin" expression might be a novel goal in treatment of chronic inflammatory skin diseases.
Original languageEnglish
Pages (from-to)e6340
JournalPloS one
Volume4
Issue number7
DOIs
Publication statusPublished - 2009

Keywords

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Blotting, Western
  • Cells, Cultured
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Interleukin-17
  • Interleukin-8
  • MAP Kinase Signaling System
  • Peptides
  • Polymerase Chain Reaction
  • Psoriasis
  • RNA Interference
  • Receptors, Calcitriol
  • Vitamin D

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