Establishment of new molecular therapy of keloid and elucidation of mechanism of development by IL-23/IL-17 pathway

我们已经报道，IL-6介导的炎症是瘢痕疙瘩发生的关键因素，可能被认为是瘢痕疙瘩发生的共同原因。IL-17是最近发现的一种促炎细胞因子，由一种独特的活化的CD4T细胞亚型Th17分泌。我们首先检测了Th17细胞在患者外周血和瘢痕疙瘩组织中的分布。与正常人相比，Th17细胞数量增加。瘢痕疙瘩成纤维细胞(KF)中IL-17基因的表达高于正常真皮成纤维细胞(NF)。我们检测了在加入IL-17A多肽后和在不同浓度的抗IL-17抗体抑制IL-17后的KF细胞中，两种主要的ECM分子COL1A2和FN1的mRNA表达。培养上清液中加入IL-17A后，COL1A2和FN1的表达呈剂量依赖性增加，而KF中的抗IL-17抗体抑制则降低COL1A2和FN1的表达。我们的结果表明，IL-17信号可能在瘢痕疙瘩的发病机制中起着不可或缺的作用，并为开发治疗或预防瘢痕疙瘩的IL-17阻断策略提供了线索。

We have reported that IL-6 mediated inflammation is a key player and may be considered as a common causative factor for development of keloid. IL-17, a recently discovered pro-inflammatory cytokine, is secreted by a distinct subtype of activated CD4 T-cells known as Th17.We first examined the distribution of Th17 cells in peripheral blood and keloid tissues obtained from the patients. There was an increased in Th17 cells as compared with normal individuals. The expression of IL-17 gene in keloid derived fibroblasts(KF) was higher than in normal dermis derived fibroblasts(NF). We measured mRNA expressions of two principal ECM molecules, COL1A2 and FN1, in NF cultures after addition of IL-17A peptide or in KF cultures after inhibition of IL-17 with anti-IL-17 antibody at various concentrations. Addition of IL-17A in NF culture medium significantly and dose-dependently enhanced COL1A2 and FN1 mRNA expressions, whereas inhibition of IL-17 by anti-IL-17 antibody in KF culture medium lowered COL1A2 and FN1 mRNA expressions. Our results indicate that IL-17 signaling may play an integral role in keloid pathogenesis and provide clues for development of IL-17 blocking strategies for therapy or prophylaxis of keloid.