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Benezeder, T; Gehad, A; Patra, V; Clark, R; Wolf, P.
Induction of IL-1β and antimicrobial peptides as a potential mechanism for topical dithranol.
Exp Dermatol. 2021; 30(6):841-846 Doi: 10.1111/exd.14310 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Leading authors Med Uni Graz
Benezeder Theresa Helena
Wolf Peter
Co-authors Med Uni Graz
Patra Vijaykumar
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Abstract:
Topical dithranol is effective in autoimmune conditions like alopecia areata, inducing hair regrowth in a high percentage of cases. Exact mechanisms of dithranol in alopecia areata, with seemingly healthy epidermis besides altered hair follicles, are not well understood. To better understand dithranol's mechanisms on healthy skin, we analysed its effect on normal murine as well as xenografted human skin. We found a strong increase in mRNA expression of anti-microbial peptides (AMPs) (eg Lcn2, Defb1, Defb3, S100a8, S100a9), keratinocyte differentiation markers (eg Serpinb3a, Flg, Krt16, Lce3e) and inflammatory cytokines (eg Il1b and Il17) in healthy murine skin. This effect was paralleled by inflammation and disturbed skin barrier, as well as an injury response resulting in epidermal hyperproliferation, as observed in murine and xenografted adult human skin. This contact response and disturbed barrier induced by dithranol might lead via a vicious loop between AMPs such as S100a8/a9 (that led to skin swelling itself after topical application) and cytokines such as IL-1β to an immune suppressive environment in the skin. A better understanding of the skin's physiologic response to dithranol may open up new avenues for the establishment of novel therapeutics (including AMP-related/interfering molecules) for certain skin conditions, such as alopecia areata.
Find related publications in this database (using NLM MeSH Indexing)
Alopecia Areata - drug therapy
Animals - administration & dosage
Anthralin - pharmacology
Antimicrobial Peptides - drug effects
Cytokines - drug effects
Dermatologic Agents - pharmacology
Humans - administration & dosage
Interleukin-1beta - drug effects
Keratinocytes - drug effects
Mice - administration & dosage
Mice, Inbred BALB C - administration & dosage

Find related publications in this database (Keywords)
alopecia areata
anthralin
cytokines
psoriasis
S100a8
a9
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