Lee Jee-Bum, Bae Soo Hyeon, Moon Ki Rang, Na Eui Young, Yun Sook Jung, Lee Seung-Chul
Department of Dermatology, Chonnam National University Medical School, Gwangju, South Korea.
Exp Dermatol. 2016 Dec;25(12):956-961. doi: 10.1111/exd.13133. Epub 2016 Oct 3.
Cathelicidin (LL-37), Toll-like receptor 2 (TLR-2) and kallikreins (KLKs) are key inflammatory mediators in rosacea. Laser or light-based devices have been successfully used for rosacea. We investigated the effects of light-emitting diodes (LEDs) on LL-37, KLKs, TLR-2 and protease activity in cultured normal human epidermal keratinocytes (NHEKs) and rosacea-like mouse skin (RLMS). LL-37, KLK5, KLK7 and vitamin D receptor were induced by 1α, 25-dihydroxyvitamin D (VD ) and TLR-2 by Ad-CMV transfection in cultured NHEKs. NHEKs were subjected to LED irradiation at differing wavelengths (480-940 nm) and fluences (1-40 J/cm ). Inflammatory mediators were analysed with RT-PCR and real-time PCR and protease activity analysis and immunocytofluorescence staining were performed for NHEKs. Changes in RLMS induced by LL-37 peptide were evaluated with real-time PCR, immunohistochemical staining and enzyme-linked immunosorbent assay. In NHEKs, LED at 630 and 940 nm significantly attenuated LL37, KLK5 and TLR-2 mRNA expressions. Protease activity was significantly suppressed at 630, 850 and 940 nm. In the RLMS, LL-37, KLK5 and PAR-2 mRNA expressions significantly decreased at 24 and 48 hours after LED irradiation was performed three times at 630 and 940 nm. mCAMP and IL-8 protein levels and protease activity after LED irradiation were lower than those in RLMS control groups. LED at 630 and 940 nm downregulated TLR-2, KLK5 and LL-37 expressions and protease activity in NHEK and RLMS. Thus, LEDs may be promising for rosacea treatment. However, clinical trials are required for further study.
抗菌肽（LL-37）、Toll样受体2（TLR-2）和激肽释放酶（KLKs）是酒渣鼻的关键炎症介质。基于激光或光的设备已成功用于治疗酒渣鼻。我们研究了发光二极管（LED）对培养的正常人表皮角质形成细胞（NHEKs）和酒渣鼻样小鼠皮肤（RLMS）中LL-37、KLKs、TLR-2和蛋白酶活性的影响。在培养的NHEKs中，1α，25-二羟基维生素D（VD）诱导LL-37、KLK5、KLK7和维生素D受体，通过Ad-CMV转染诱导TLR-2。将NHEKs置于不同波长（480-940nm）和能量密度（1-40J/cm²）的LED照射下。用RT-PCR和实时PCR分析炎症介质，并对NHEKs进行蛋白酶活性分析和免疫细胞荧光染色。用实时PCR、免疫组织化学染色和酶联免疫吸附测定评估LL-37肽诱导的RLMS变化。在NHEKs中，630和940nm的LED显著减弱LL37、KLK5和TLR-2 mRNA表达。在630、850和940nm处蛋白酶活性显著受到抑制。在RLMS中，在630和940nm处进行三次LED照射后24和48小时，LL-37、KLK5和PAR-2 mRNA表达显著降低。LED照射后的mCAMP和IL-8蛋白水平以及蛋白酶活性低于RLMS对照组。630和940nm的LED下调NHEK和RLMS中TLR-2、KLK5和LL-37的表达以及蛋白酶活性。因此，LED可能有望用于酒渣鼻治疗。然而，需要进行临床试验以作进一步研究。
