Induction of apoptosis by Toll-like receptor-7 agonist in tissue cultures

Meyer, Thomas; Nindl, Ingo; Schmook, Tobias; Ulrich, Claas; Sterry, Wolfram; Stockfleth, Eggert

doi:10.1046/j.0366-077x.2003.05632.x

Cited by 78 publications

(63 citation statements)

References 17 publications

(17 reference statements)

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“…However, imiquimod exerts an additional direct proapoptotic activity against tumor cells (Scho¨n et al, 2003), a surprising observation that was confirmed in vivo in tumors of different origin (Sidbury et al, 2003;Sullivan et al, 2003;Scho¨n et al, 2004;Vidal et al, 2004) as well as on the cellular level in vitro (Meyer et al, 2003). While the proapoptotic activity of imiquimod is independent of membrane-bound death receptors, shifts of Bcl-2 proteins in favor of the proapoptotic Bax were observed.…”

Section: Proapoptotic Activity Of Imiquimodmentioning

confidence: 95%

TLR7 and TLR8 as targets in cancer therapy

2008

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Small-molecule agonists at Toll-like receptor 7 (TLR7) and TLR8 have sparked a vivid interest in cancer research owing to their profound antitumoral activity. The lead compound of the imidazoquinoline family, imiquimod, is marketed as a topical formulation. It is efficacious against many primary skin tumors and cutaneous metastases. Using different imidazoquinoline species, distinct functions of TLR7 and TLR8 have been discovered. The predominant antitumoral mode of action of these agents is TLR7/ 8-mediated activation of the central transcription factor nuclear factor-jB, which leads to induction of proinflammatory cytokines and other mediators. Cutaneous dendritic cells are the primary responsive cell type and initiate a strong Th1-weighted antitumoral cellular immune response. Recent research has shown that dendritic cells themselves acquire direct antitumoral activity upon stimulation by imiquimod. In addition, there are a number of secondary effects on the molecular and cellular level that can be explained through the activation of TLR7/8. The proinflammatory activity of imiquimod, but not resiquimod, appears to be augmented by suppression of a regulatory mechanism, which normally limits inflammatory responses. This is achieved independently of TLR7/8 through interference with adenosine receptor signaling pathways. Finally, at higher concentrations imiquimod exerts Bcl-2-and caspase-dependent proapoptotic activity against tumor cells.

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Section: Proapoptotic Activity Of Imiquimodmentioning

confidence: 95%

TLR7 and TLR8 as targets in cancer therapy

2008

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“…It was shown in vitro that imiquimod can directly induce apoptosis of tumor cells using several skin and bladder cancer cells lines, as well as tumor tissue cultures [97][98][99][100][101]. For the skin cancer cell lines, it was demonstrated that this proapoptotic activity was independent of membrane-bound death receptors.…”

Section: Tumor Cellsmentioning

confidence: 99%

The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy

et al. 2008

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After completing this course, the reader should be able to:1. Describe the subtypes of Toll-like receptor 7 and 8 agonists and their effect on the different components of the antitumor immune response.2. Argue why they are used as stand-alone immunotherapeutic agents.3. Evaluate their potential to improve current approaches of active and passive immunotherapy.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACT

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“…It was reported that imiquimod induced apoptosis of human epithelial cells, keratinocytes, and mouse Wbroblasts [8,15]. Topical application of imiquimod cream to keloids alters expression of genes associated with apoptosis including caspase-3 [9].…”

Section: Introductionmentioning

confidence: 99%

Imiquimod induces apoptosis of human melanocytes

et al. 2009

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Development of vitiligo-like hypopigmentary lesions associated with topical imiquimod has been reported. We hypothesized that mode of action of imiquimod in melanocytes may include triggering of apoptosis resulted in loss of cells, which may be a possible mechanism of imiquimod-induced hypopigmentary lesions. Therefore, we investigated whether imiquimod induces apoptosis of human melanocytes and also whether it modulates expression of apoptosis-related molecules in human melanocytes. Imiquimod treatment induced apoptosis of melanocytes, which was observed by TUNEL assay and Hoechst 33258 staining. Imiquimod-induced apoptosis was further shown by measuring mitochondrial membrane potential in melanocytes. The apoptotic activity of imiquimod was associated with caspase-3, Bcl-2 and mitogenactivated protein kinase expression in melanocytes. These results indicated that imiquimod induces apoptosis of melanocytes. These Wndings may provide a clue to understand pathogenesis of imiquimod-induced vitiligo-like hypopigmentary lesions.

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Induction of apoptosis by Toll-like receptor-7 agonist in tissue cultures

Cited by 78 publications

References 17 publications

TLR7 and TLR8 as targets in cancer therapy

TLR7 and TLR8 as targets in cancer therapy

The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy

Imiquimod induces apoptosis of human melanocytes

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