Vitamin D Analogs Differentially Control Antimicrobial Peptide/"Alarmin" Expression in Psoriasis

被引:102
作者
Peric, Mark
Koglin, Sarah
Dombrowski, Yvonne
Gross, Katrin
Bradac, Eva
Buechau, Amanda
Steinmeyer, Andreas
Zuegel, Ulrich
Ruzicka, Thomas
Schauber, Juergen
机构
[1] Department of Dermatology and Allergology, Ludwig-Maximilians-University, Munich
[2] Common Mechanism Research Early Projects, Global Drug Discovery, Bayer Schering Pharma AG, Berlin
[3] Department of Medicinal Chemistry, Global Drug Discovery, Bayer Schering Pharma AG, Berlin
来源
PLOS ONE | 2009年 / 4卷 / 07期
关键词
D O I
10.1371/journal.pone.0006340
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 I kappa B-alpha protein and inhibition of NF-kappa B 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.
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页数:10
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