The Henna pigment Lawsone activates the Aryl Hydrocarbon Receptor and impacts skin homeostasis

被引:23
作者
Lozza, Laura [1 ]
Moura-Alves, Pedro [1 ,2 ]
Domaszewska, Teresa [1 ]
Crespo, Carolina Lage [3 ]
Streata, Ioana [4 ]
Kreuchwig, Annika [5 ]
Puyskens, Andreas [1 ]
Bechtle, Marina [1 ]
Klemm, Marion [1 ]
Zedler, Ulrike [1 ]
Ungureanu, Bogdan Silviu [6 ]
Guhlich-Bornhof, Ute [1 ]
Koehler, Anne-Britta [1 ]
Staeber, Manuela [1 ]
Mollenkopf, Hans-Joachim [7 ]
Hurwitz, Robert [8 ]
Furkert, Jens [5 ]
Krause, Gerd [5 ]
Weiner, January, III [1 ]
Jacinto, Antonio [3 ]
Mihai, Ioana [4 ]
Leite-de-Moraes, Maria [9 ,10 ]
Siebenhaar, Frank [11 ]
Maurer, Marcus [11 ]
Kaufmann, Stefan H. E. [1 ,12 ]
机构
[1] Max Planck Inst Infect Biol, Dept Immunol, Charitepl 1, D-10117 Berlin, Germany
[2] Univ Oxford, Ludwig Inst Canc Res, Nuffield Dept Clin Med, Oxford, England
[3] NOVA Univ Lisbon, NOVA Med Sch, CEDOC, P-1169056 Lisbon, Portugal
[4] Univ Med & Pharm Craiova, Human Genom Lab, Craiova, Romania
[5] Leibniz Forschungsinst Mol Pharmakol FMP, Robert Rossle Str 10, D-13125 Berlin, Germany
[6] Univ Med & Pharm Craiova, Res Ctr Gastroenterol & Hepatol, Craiova, Romania
[7] Max Planck Inst Infect Biol, Microarray Core Facil, Charitepl 1, D-10117 Berlin, Germany
[8] Max Planck Inst Infect Biol, Biochem & Prot Purificat Core Facil, Charitepl 1, D-10117 Berlin, Germany
[9] CNRS UMR8253, INSERM UMR1151, INEM, Lab Immunoregulat & Immunopathol, Paris, France
[10] Paris Descartes Univ, Paris, France
[11] Charite Univ Med Berlin, Dept Dermatol & Allergy, Berlin, Germany
[12] Texas A&M Univ, Hagler Inst Adv Study, College Stn, TX 77843 USA
关键词
KERATINOCYTES; EXPRESSION; DIOXIN; AHR; DIFFERENTIATION; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; IDENTIFICATION; DERMATITIS; INDUCTION; TOXICITY;
D O I
10.1038/s41598-019-47350-x
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
As a first host barrier, the skin is constantly exposed to environmental insults that perturb its integrity. Tight regulation of skin homeostasis is largely controlled by the aryl hydrocarbon receptor (AhR). Here, we demonstrate that Henna and its major pigment, the naphthoquinone Lawsone activate AhR, both in vitro and in vivo. In human keratinocytes and epidermis equivalents, Lawsone exposure enhances the production of late epidermal proteins, impacts keratinocyte differentiation and proliferation, and regulates skin inflammation. To determine the potential use of Lawsone for therapeutic application, we harnessed human, murine and zebrafish models. In skin regeneration models, Lawsone interferes with physiological tissue regeneration and inhibits wound healing. Conversely, in a human acute dermatitis model, topical application of a Lawsone-containing cream ameliorates skin irritation. Altogether, our study reveals how a widely used natural plant pigment is sensed by the host receptor AhR, and how the physiopathological context determines beneficial and detrimental outcomes.
引用
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页数:21
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