Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin - 30/03/13
, Michel Simon, PhD a, b, c, ⁎ 
Corresponding author: Michel Simon, PhD, CNRS-UPS UMR5165, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse cedex 9, France.Abstract |
Background |
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a disturbed epidermal barrier. In a subset of patients, this is explained by nonsense mutations in the gene encoding filaggrin (FLG).
Objectives |
We sought to evaluate the respective role of FLG mutations and proinflammatory cytokines and to assess the expression of FLG, hornerin (HRNR), and FLG2, 2 FLG-like proteins, which are involved in epidermal barrier functions, in normal skin and both lesional and nonlesional skin of patients with AD.
Methods |
An FLG-genotyped cohort of 73 adults with AD and 73 aged-matched control subjects was analyzed by using immunohistochemistry and immunoblotting. Normal primary human keratinocytes were differentiated in either the absence or presence of IL-4, IL-13, and IL-25.
Results |
Compared with control subjects, FLG, HRNR, and FLG2 were detected at significantly lower levels in the skin of patients with AD, irrespective of their FLG genotype. The reduction was greater in lesional compared with nonlesional skin. In addition, the proFLG/FLG ratio was found to be higher in the skin of wild-type patients than in control subjects. Cytokine treatment of keratinocytes induced a dramatic reduction in FLG, FLG2, and HRNR expression both at the mRNA and protein levels.
Conclusion |
The stratum corneum of lesional but also clinically unaffected skin of adults with AD is abnormal, with reduced expression of FLG and FLG-like proteins. In addition to nonsense mutations, proinflammatory cytokines and some defects in the proFLG processing can contribute to the FLG downregulation. Our study suggests that skin inflammation reduces the expression of FLG-like proteins, contributing to the AD-related epidermal barrier dysfunction.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, skin, keratinocytes, filaggrin, hornerin, stratum corneum, skin barrier, cytokine
Abbreviations used : AD, FLG, HRNR, OR, qPCR, TEWL
Plan
| Supported by grants from CNRS, Toulouse University, INSERM, Pierre-Fabre Dermo-Cosmetique, Société de Recherche Dermatologique (SRD) and the French Society for Dermatology (SFD), and the European COST program “SKINBAD” (action BM0903). |
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| Disclosure of potential conflict of interest: J. Henry, C.-Y. Hsu, S. Balica, C. Jean-Decoster, B. Hansmann, E. Rodriguez, and M. Simon have been supported by one or more grants from Pierre Fabre Dermo-Cosmétique, Société de Recherche Dermatologique, and Société Française de Dermatologie and has received support for travel from European COST program “SKINBAD” (action BM0903). S. Weindinger is a Board member for Allergy; has consultancy arrangements with Novartis, Astellas, and Danone; and has received one or more grants from or has one or more grants pending with DFG, BMBF. C. Paul has been supported by one or more grants from Pierre Fabre; is a Board member for Pierre Fabre, Astellas, Abbott, and Celgene; has consultancy arrangements with Janssen, Novartis, Pfizer, and Sanofi; has provided expert testimony for Astellas; has received one or more grants from or has one or more grants pending with Abbott; has received one or more payments for lecturing from or is on the speakers’ bureau for Abbott, Janssen, and Astellas; and has received one or more payments for the development of educational presentations for Novartis. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 4
P. 1094-1102 - avril 2013 Retour au numéro
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