Department of Medical Science, Soonchunhyang University, Asan, Chungnam, 31538, Republic of Korea.
Department of Medical Science, Soonchunhyang University, Asan, Chungnam, 31538, Republic of Korea; Department of Medical Biotechnology, Soonchunhyang University, Asan, Chungnam, 31538, Republic of Korea.
Photodiagnosis Photodyn Ther. 2017 Dec;20:71-77. doi: 10.1016/j.pdpdt.2017.08.002. Epub 2017 Aug 12.
Photodynamic therapy (PDT) is a clinically approved therapeutic for cancers and non-neoplastic diseases, based on the use of a photosensitizer activated by light. The feasibility of PDT depends on several factors, such as PDT dose, photosensitizer efficacy, type of light source, and target tissue irradiated.
In this study, the second generation photosensitizer chlorin e6 (Ce6) and halogen light were used to investigate their PDT effect on the collagen production and MMPs expression of heat killed P. acnes-stimulated HaCaT cells. The mRNA levels of COL1A1, c-Jun, and c-Fos were detected by RT-PCR. The protein levels of MMPs, ERK and JNK were detected by western blot. The transactivation of AP-1 was detected by luciferase assay.
Ce6-based PDT markedly upregulated the mRNA level of COL1A1 and type I procollagen level; and at the same time downregulated the expression of MMPs in P. acnes-infected HaCaT cells. Moreover, Ce6-mediated PDT, in a dose dependent manner, inhibited P. acnes-induced phosphorylation of JNK and ERK, as wells as the phosphorylation of their downstream targets c-Jun and c-Fos. P. acnes-induced mRNA expression of c-Jun and c-Fos were also suppressed by Ce6-mediated PDT. The transactivation of AP-1 induced by P. acnes infection was also downregulated.
These results indicated that Ce6-mediated PDT with halogen light enhanced collagen production, but inhibited the expression of MMPs in P. acnes-infected HaCaT cells, by regulating AP-1 signals. This investigation provided the first molecular basis for the increase in collagen production by Ce6-mediated PDT, suggesting its potential use for scar amelioration and skin rejuvenation in acne treatment.
光动力疗法（PDT）是一种基于光敏剂在光激活下被用于治疗癌症和非肿瘤性疾病的临床批准疗法。PDT 的可行性取决于几个因素，例如 PDT 剂量、光敏剂效力、光源类型和被辐照的靶组织。
在这项研究中，使用第二代光敏剂氯乙酮（Ce6）和卤素光来研究它们对热死痤疮丙酸杆菌刺激的 HaCaT 细胞胶原产生和 MMPs 表达的 PDT 效应。通过 RT-PCR 检测 COL1A1、c-Jun 和 c-Fos 的 mRNA 水平。通过 Western blot 检测 MMPs、ERK 和 JNK 的蛋白水平。通过荧光素酶测定法检测 AP-1 的转激活。
Ce6 基 PDT 显著上调 COL1A1 的 mRNA 水平和 I 型前胶原水平；同时下调 P. acnes 感染的 HaCaT 细胞中 MMPs 的表达。此外，Ce6 介导的 PDT 以剂量依赖性方式抑制了 P. acnes 诱导的 JNK 和 ERK 的磷酸化，以及其下游靶标 c-Jun 和 c-Fos 的磷酸化。Ce6 介导的 PDT 还抑制了 P. acnes 诱导的 c-Jun 和 c-Fos 的 mRNA 表达。P. acnes 感染诱导的 AP-1 转激活也被下调。
这些结果表明，Ce6 介导的 PDT 与卤素光一起增强了 P. acnes 感染的 HaCaT 细胞中的胶原产生，但抑制了 MMPs 的表达，通过调节 AP-1 信号。这项研究为 Ce6 介导的 PDT 增加胶原产生提供了第一个分子基础，表明其在痤疮治疗中改善疤痕和皮肤年轻化方面具有潜在用途。
