Induction of apoptosis by Toll-like receptor-7 agonist in tissue cultures
Induction of apoptosis by Toll-like receptor-7 agonist in tissue cultures
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DOI：
10.1046/j.0366-077x.2003.05632.x
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发表时间：
2003-11-01
影响因子：
10.3
通讯作者：
Stockfleth, E
中科院分区：
文献类型：
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作者：
Meyer, T;Nindl, I;Stockfleth, E
toll样受体(TLR)-7激动剂是一类新的免疫反应调节剂，包括咪喹莫特和雷昔莫特（R-848）。局部应用咪喹莫特用于治疗外生殖器疣和肛周生殖器疣，以及良性和恶性上皮病变。基于干扰素和其他细胞因子在体外和体内的诱导作用，上皮病变的消退可能依赖于先天和细胞免疫反应的诱导。由于临床缓解并不总是与炎症有关，其他机制也可能参与其中。采用两种不同的细胞凋亡检测方法（TUNEL试验和DNA片段凝胶分析），我们观察到咪喹莫特诱导人上皮细胞系（HeLa S3）、角质形成细胞（HaCaT、A431细胞）以及小鼠成纤维细胞（McCoy细胞）凋亡。这些发现表明，咪喹莫特消除病毒感染、发育不良或肿瘤上皮细胞的作用模式也可能包括诱导凋亡过程。
Toll-like receptor (TLR)-7 agonists represent a new group of immune response modifiers, which include imiquimod and resiquimod (R-848). Topically applied imiquimod is used for the treatment of both external and perianal genital warts, and benign and malignant epithelial lesions. Based on the induction of interferons and other cytokines in vitro and in vivo, regression of epithelial lesions probably depends on induction of both innate and cellular immune responses. As clinical remission is not always associated with inflammation, other mechanisms may also be involved. Using two different assays for detection of apoptosis (TUNEL test and gel analysis of DNA fragmentation), we observed induction of apoptosis by imiquimod in human epithelial cell lines (HeLa S3) and keratinocytes (HaCaT, A431 cells), as well as in mouse fibroblasts (McCoy cells). These findings suggest that the mode of action of imiquimod to eliminate virus-infected, dysplastic or neoplastic epithelial cells may also include the induction of apoptotic processes.