Induction of apoptosis by Toll-like receptor-7 agonist in tissue cultures.
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.
Meyer
T
T
Institute of Immunology, Clinical Pathology and Molecular Medicine, Lademannbogen 61, 22339 Hamburg, Germany. meyer@labor-arndt-partner.de
Nindl
I
I
Schmook
T
T
Ulrich
C
C
Sterry
W
W
Stockfleth
E
E
D000634:Aminoquinolines / Q000494:pharmacology*; D017209:Apoptosis; D002460:Cell Line; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D018922:HL-60 Cells / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D000077271:Imiquimod; D007155:Immunologic Factors / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology; D008562:Membrane Glycoproteins / Q000819:agonists*; D011956:Receptors, Cell Surface / Q000819:agonists*; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors
D000634:Aminoquinolines; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors; D000077271:Imiquimod