Aldara activates TLR7-independent immune defence

被引：200

作者：

Walter, Anne ^{[1
]}

Schaefer, Matthias ^{[2
]}

Cecconi, Virginia ^{[1
]}

Matter, Claudia ^{[1
]}

Urosevic-Maiwald, Mirjana ^{[3
]}

Belloni, Benedetta ^{[3
]}

Schoenewolf, Nicola ^{[3
]}

Dummer, Reinhard ^{[3
]}

Bloch, Wilhelm ^{[4
]}

Werner, Sabine ^{[2
]}

Beer, Hans-Dietmar ^{[3
]}

Knuth, Alexander ^{[1
]}

van den Broek, Maries ^{[1
]}

机构：

[1] Univ Zurich Hosp, Dept Oncol, CH-8952 Schlieren, Switzerland

[2] ETH, Inst Mol Hlth Sci, Dept Biol, CH-8093 Zurich, Switzerland

[3] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland

[4] German Sport Univ Cologne, Dept Mol & Cellular Sport Med, D-50933 Cologne, Germany

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

基金：

瑞士国家科学基金会;

关键词：

BASAL-CELL CARCINOMA; ROR-GAMMA-T; RESPONSE MODIFIER; SQUAMOUS-CELL; IMIQUIMOD; RECEPTOR; MICE; INFLAMMATION; GENERATION; EXPRESSION;

D O I：

10.1038/ncomms2566

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

共 53 条

[1] Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].