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PMID: 23463003 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Aldara activates TLR7-independent immune defence.

Nature communications ·Vol. 4 ·2013-00-00 ·Pages 1560

Walter A, Schäfer M, Cecconi V, Matter C, Urosevic-Maiwald M, Belloni B, Schönewolf N, Dummer R, Bloch W, Werner S, Beer HD, Knuth A, van den Broek M

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.

MeSH Terms
Aminoquinolines/adverse effects,pharmacology,therapeutic use Animals Apoptosis/drug effects Carcinoma, Basal Cell/drug therapy,immunology,pathology Cell Proliferation/drug effects Cells, Cultured Cytokines/metabolism Epidermis/drug effects,immunology,pathology,ultrastructure Gene Expression Regulation/drug effects Humans Imiquimod Immunity/drug effects,immunology Inflammasomes/metabolism Interferon Type I/immunology Keratinocytes/drug effects,immunology,pathology Keratosis, Actinic/drug therapy,immunology,pathology Mice Models, Immunological Neutrophil Infiltration/drug effects RNA, Messenger/genetics,metabolism Skin Neoplasms/drug therapy,immunology,pathology Toll-Like Receptor 7/immunology Up-Regulation/drug effects
Chemicals
Aminoquinolines Cytokines Inflammasomes Interferon Type I RNA, Messenger Toll-Like Receptor 7 Imiquimod
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Walter Anne
Department of Oncology, University Hospital Zurich, Wagistrasse 14, 8952 Schlieren, Switzerland.
Schäfer Matthias
Cecconi Virginia
Matter Claudia
Urosevic-Maiwald Mirjana
Belloni Benedetta
Schönewolf Nicola
Dummer Reinhard
Bloch Wilhelm
Werner Sabine
Beer Hans-Dietmar
Knuth Alexander
van den Broek Maries
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms2566
Published
2013-00-00
Pages
1560
Language
English
Region
England
NLM ID
101528555
Subset
IM
External Links
PubMed source DOI: 10.1038/ncomms2566 View journal details
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