Borovaya Alena, Dombrowski Yvonne, Zwicker Stephanie, Olisova Olga, Ruzicka Thomas, Wolf Ronald, Schauber Jürgen, Sárdy Miklós
Department of Dermatology and Allergology, Ludwig Maximilian University Munich, Frauenlobstr. 9-11, 80337, Munich, Germany.
Arch Dermatol Res. 2014 Oct;306(8):689-700. doi: 10.1007/s00403-014-1477-3. Epub 2014 Jun 11.
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 β-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas α-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.
在寻常痤疮中，抗菌肽（AMPs）可能发挥双重作用；即通过对抗痤疮丙酸杆菌起到保护作用，又作为信号分子发挥促炎作用。研究了痤疮患者中15种不同抗菌肽的皮肤表达情况；此外，使用定量实时聚合酶链反应分析了异维A酸治疗对13例寻常痤疮患者皮肤活检样本中抗菌肽表达的影响，这些活检样本取自异维A酸6个月治疗周期之前、期间和之后。在未经治疗的寻常痤疮中，抗菌肽cathelicidin、人β-防御素-2（HBD-2）、乳铁蛋白、溶菌酶、银屑素（S100A7）、柯布纳素（S100A15）和核糖核酸酶7的皮肤表达上调，而与对照组相比，α-防御素-1（HNP-1）表达下调。在异维A酸治疗期间，cathelicidin、HBD-2、乳铁蛋白、银屑素（S100A7）和柯布纳素（S100A15）的相对表达水平下降，但异维A酸治疗6个月后，只有cathelicidin和柯布纳素的表达恢复正常。溶菌酶和核糖核酸酶7表达的增加不受异维A酸治疗的影响。颗粒溶素、调节激活正常T细胞表达和分泌因子（RANTES，CCL5）、穿孔素、CXCL9、P物质、嗜铬粒蛋白B和皮肤杀菌肽的水平在未经治疗的痤疮患者中未受调节，异维A酸对这些抗菌肽也没有影响。总之，寻常痤疮中各种抗菌肽的表达发生了改变。异维A酸治疗可使不同抗菌肽的皮肤产生恢复正常，而在愈合中的痤疮中，其他一些抗菌肽的表达仍会增加。考虑到抗菌肽的抗菌和促炎作用，这些分子可作为痤疮治疗和维持临床缓解的特定靶点。
