title: Aldara activates TLR7-independent immune defence.
abstract: Aldara is a cream used for topical treatment of non-melanoma skin cancer, and is thought to act through stimulation of anti-tumour immunity. The active ingredient, imiquimod, has been shown to stimulate toll-like receptor 7. Aldara also induces psoriasis-like lesions when applied to naive murine skin, and as such is used as a mouse model for psoriasis. Here we find that in naive murine skin, Aldara induces inflammation largely independently of toll-like receptor 7. Surprisingly, inflammasome activation, keratinocyte death and interleukin 1 release also occur in response to the vehicle cream in the absence of imiquimod. We show that isostearic acid, a major component of the vehicle, promotes inflammasome activation in cultured keratinocytes, and so may contribute to the observed effects of Aldara on murine skin. Aldara therefore stimulates at least two immune pathways independently, and both imiquimod and vehicle are required for a full inflammatory response. Although it remains to be tested, it is possible that imiquimod-independent effects also contribute to the therapeutic efficacy of Aldara.
authors: Department of Oncology, University Hospital Zurich, Wagistrasse 14, 8952 Schlieren, Switzerland.
authors: Anne
authors: A
authors: Walter
authors: Matthias
authors: M
authors: Schäfer
authors: Virginia
authors: V
authors: Cecconi
authors: Claudia
authors: C
authors: Matter
authors: Mirjana
authors: M
authors: Urosevic-Maiwald
authors: Benedetta
authors: B
authors: Belloni
authors: Nicola
authors: N
authors: Schönewolf
authors: Reinhard
authors: R
authors: Dummer
authors: Wilhelm
authors: W
authors: Bloch
authors: Sabine
authors: S
authors: Werner
authors: Hans-Dietmar
authors: HD
authors: Beer
authors: Alexander
authors: A
authors: Knuth
authors: Maries
authors: M
authors: van den Broek
mesh_terms: D000634:Aminoquinolines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002280:Basal Cell Carcinoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000077271:Imiquimod; D007109:Immunity / Q000187:drug effects* / Q000276:immunology*; D058847:Inflammasomes / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D055623:Keratosis, Actinic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051379:Mice; D018448:Models, Immunological; D020556:Neutrophil Infiltration / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D058847:Inflammasomes; D007370:Interferon Type I; D012333:RNA, Messenger; D051199:Toll-Like Receptor 7; D000077271:Imiquimod