Vitamin D analogs differentially control antimicrobial peptide/"alarmin" expression in psoriasis.
Vitamin D analogs differentially control antimicrobial peptide/"alarmin" expression in psoriasis.
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DOI：
10.1371/journal.pone.0006340
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发表时间：
2009-07-22
期刊：
影响因子：
3.7
通讯作者：
Schauber J
中科院分区：
文献类型：
--
作者：
Peric M;Koglin S;Dombrowski Y;Gross K;Bradac E;Büchau A;Steinmeyer A;Zügel U;Ruzicka T;Schauber J
抗菌肽（AMPs）在牛皮癣病变皮肤中强烈表达，在这种慢性皮肤病中起着促炎“警报器”的重要作用。维生素D类似物如钙化三醇具有抗银屑病作用，可能通过改变AMP表达介导这种作用。在本研究中，病灶性银屑病斑块中的角化细胞在局部用钙三醇治疗后显示AMPs β-防御素（HBD） 2和HBD3的表达降低。同时，钙化三醇使促炎细胞因子环境正常化，并降低病变银屑病皮肤中白细胞介素(IL)-17A、IL- 17f和IL-8转录物丰度。相比之下，钙化三醇增加了抗菌肽cathelicidin的表达，而牛皮癣蛋白的表达保持不变。在体外培养的人表皮角质形成细胞中，进一步分析不同维生素D类似物对amp表达的影响。所有维生素D类似物通过增加i -κB -α蛋白和抑制NF-κB信号传导来阻断IL-17A诱导的HBD2表达。同时，维生素D类似物通过激活维生素D受体和MEK/ERK信号传导诱导抗菌肽。这些研究表明，维生素D类似物在病变性银屑病皮肤和培养的角化细胞中改变AMP的表达存在差异。平衡AMP“警报蛋白”的表达可能是治疗慢性炎症性皮肤病的新目标。
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.
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