Isotretinoin therapy changes the expression of antimicrobial peptides in acne vulgaris
Isotretinoin therapy changes the expression of antimicrobial peptides in acne vulgaris
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DOI：
10.1007/s00403-014-1477-3
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发表时间：
2014-10-01
影响因子：
3
通讯作者：
Sardy, Miklos
中科院分区：
文献类型：
--
作者：
Borovaya, Alena;Dombrowski, Yvonne;Sardy, Miklos
在寻常痤疮中，抗微生物肽（AMP）可以发挥双重作用;即，通过对抗痤疮丙酸杆菌而具有保护作用，通过充当信号分子而具有促炎作用。研究了痤疮患者皮肤中15种不同AMP的表达;此外，采用实时定量聚合酶链反应分析了异维甲酸治疗对13例寻常痤疮患者皮肤活检中AMP表达的影响，这些患者在异维甲酸6个月治疗周期之前、期间和之后接受治疗。与对照组相比，未治疗的寻常痤疮中抗菌肽cathelicidin、人β-防御素-2（HBD-2）、乳铁蛋白、溶菌酶、银屑病菌素（S100 A7）、Koebnerisin（S100 A15）和RNase 7的皮肤表达上调，而α-防御素-1（HNP-1）下调。虽然cathelicidin，HBD-2，乳铁蛋白，银屑病（S100 A7）和koebnerisin（S100 A15）的相对表达水平在异维A酸治疗期间下降，但只有cathelicidin和koebnerisin在异维A酸治疗6个月后恢复正常。溶菌酶和RNase 7的表达增加不受异维A酸处理的影响。未经治疗的痤疮患者的颗粒溶解素、RANTES（CCL 5）、穿孔素、CXCL 9、P物质、嗜铬粒蛋白B和杀皮素水平不受调节，异维甲酸对这些AMP没有影响。总之，各种AMP的表达在寻常痤疮中改变。异维A酸治疗使皮肤产生不同的AMP正常化，而其他AMP的表达在愈合痤疮中仍然增加。考虑到抗菌肽的抗菌和促炎作用，这些分子可以作为痤疮治疗和维持临床缓解的特异性靶点。
In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e., protective by acting against Propionibacterium acnes, pro-inflammatory by acting as signalling molecules. The cutaneous expression of 15 different AMPs was investigated in acne patients; furthermore, the impact of isotretinoin therapy on AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris taken before, during and after a 6-month treatment cycle with isotretinoin using quantitative real-time polymerase chain reaction. Cutaneous expression of the AMPs cathelicidin, human beta-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas alpha-defensin-1 (HNP-1) was downregulated compared to controls. While relative expression levels of cathelicidin, HBD-2, lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during isotretinoin treatment, only those of cathelicidin and koebnerisin returned to normal after 6 months of isotretinoin therapy. The increased expression of lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and dermcidin were not regulated in untreated acne patients and isotretinoin had no effect on these AMPs. In conclusion, the expression of various AMPs is altered in acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of distinct AMPs while the expression of others is still increased in healing acne. Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules could serve as specific targets for acne therapy and maintenance of clinical remission.