Professor Dr. med. Eggert Stockfleth
Apoptoseinduktion durch Toll-like-Rezeptoren-7-Agonisten bei Keratinozyten und Fibroblasten in der Gewebekultur
Klinik
für Dermatologie, Universitätsklinikum Charité, Berlin
unter Mitarbeit von Thomas Meyer, IPM Hamburg
Toll like receptor 7 (TLR7) agonists represent a new
group of immune response modifiers including imiquimod and resiquimod (R-848).
Topically applied imiquimod was used for the treament of both 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. Since 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.
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