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

瘢痕疙瘩新分子疗法的建立及IL-23/IL-17通路发展机制的阐明

• 批准号: 21592298
• 负责人: TOSA Mamiko
• 金额: $ 2.91万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592298/
• 关键词: ケロイド; IL-17; IL-23; ケロイドモデル; 培養細胞; Th17

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.

我们已经报道了IL-6介导的炎症是一个关键的球员，并可能被认为是一个共同的致病因素发展的瘢痕疙瘩。IL-17是新近发现的一种促炎细胞因子，由活化的CD 4 T细胞Th 17分泌。与正常人相比，Th 17细胞有所增加。IL-17基因在瘢痕疙瘩成纤维细胞（KF）中的表达高于正常真皮成纤维细胞（NF）。我们在NF培养物中加入IL-17 A肽后或在KF培养物中用不同浓度的抗IL-17抗体抑制IL-17后，测量了两种主要ECM分子COL 1A 2和FN 1的mRNA表达。NF培养液中加入IL-17 A可显著增加COL 1A 2和FN 1 mRNA的表达，并呈剂量依赖性;而KF培养液中加入抗IL-17抗体抑制IL-17可降低COL 1A 2和FN 1 mRNA的表达。我们的研究结果表明，IL-17信号转导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IL-17阻断策略治疗或预防瘢痕疙瘩提供线索。

项目成果

ケロイドにおけるTh17細胞のIL-6シグナル促進効果の検討

Th17细胞在瘢痕疙瘩中IL-6信号促进作用的检测

• 发表时间: 2010
• 作者: 土佐眞美子;モハマッド・ガジザデ
• 通讯作者: モハマッド・ガジザデ