Vitamin D Analogs Differentially Control Antimicrobial Peptide/“Alarmin”Expression in Psoriasis
Open Access
- 22 July 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (7), e6340
- https://doi.org/10.1371/journal.pone.0006340
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 β-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 IκB-α protein and inhibition of NF-κB 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.Keywords
This publication has 45 references indexed in Scilit:
- Psoriasis Is Characterized by Accumulation of Immunostimulatory and Th1/Th17 Cell-Polarizing Myeloid Dendritic CellsJournal of Investigative Dermatology, 2009
- Administration of oral vitamin D induces cathelicidin production in atopic individualsJournal of Allergy and Clinical Immunology, 2008
- Antimicrobial peptides and the skin immune defense systemJournal of Allergy and Clinical Immunology, 2008
- Requirements for Two Proximal NF-κB Binding Sites and IκB-ζ in IL-17A-induced Human β-Defensin 2 Expression by Conducting Airway EpitheliumJournal of Biological Chemistry, 2008
- Histone Acetylation in Keratinocytes Enables Control of the Expression of Cathelicidin and CD14 by 1,25-Dihydroxyvitamin D3Journal of Investigative Dermatology, 2008
- Microbicidal protein psoriasin is a multifunctional modulator of neutrophil activationImmunology, 2008
- Psoriasis is associated with increased β-defensin genomic copy numberNature Genetics, 2007
- Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responsesThe Journal of Experimental Medicine, 2007
- A role for T cell-derived interleukin 22 in psoriatic skin inflammationClinical and Experimental Immunology, 2007
- Development, cytokine profile and function of human interleukin 17–producing helper T cellsNature Immunology, 2007