Archives of Dermatological Research

, Volume 304, Issue 4, pp 289–303

Studies of cell signaling in a reconstructed human epidermis exposed to sensitizers: IL-8 synthesis and release depend on EGFR activation

  • Aurélie Frankart
  • Alain Coquette
  • Klaus-Rudolf Schroeder
  • Yves Poumay
Original Paper

DOI: 10.1007/s00403-012-1209-5

Cite this article as:
Frankart, A., Coquette, A., Schroeder, KR. et al. Arch Dermatol Res (2012) 304: 289. doi:10.1007/s00403-012-1209-5

Abstract

Models of reconstructed human epidermis (RHE) holding proliferating and fully differentiated cultured keratinocytes allow in vitro investigation of early molecular and cellular epidermal events during the complex response of keratinocytes at the onset of allergic contact dermatitis (ACD) or sensitization. In this study, data collected on RHE exposed to well-characterized sensitizing chemicals, such as dinitrofluorobenzene, oxazolone, cinnamaldehyde and isoeugenol, revealed a transient expression of IL-8 mRNA in association with abundant IL-8 cell release. Investigations of keratinocyte signaling illustrate transient activation by tissue exposure to sensitizing chemicals of the epidermal growth factor receptor (EGFR). This activation of EGFR tyrosine kinase is involved in the expression and release of IL-8. The IL-8 release appears also to be partially dependent on p38 and ERK 1/2 MAPK activation. Moreover, data suggest that heparin-binding EGF-like growth factor (HB-EGF) expression and release induced after exposure of RHE to sensitizing chemicals are also under the control of EGFR tyrosine kinase activity, independently of the IL-8 expression and release. Mechanistic approach of keratinocyte responses in the context of RHE underlying regulation of expression and release of epidermal cytokines and growth factors after topical application of sensitizing chemicals is proposed to identify biomarkers which could then be analysed for in vitro toxicological screening of new or undefined compounds.

Keywords

Keratinocytes RHE (reconstructed human epidermis) Sensitizers IL-8 EGFR signaling 

Abbreviations

AD

Atopic dermatitis

ACD

Allergic contact dermatitis

BC

Benzalkonium chloride

Cin

Cinnamaldehyde

DC

Dendritic cell

DNFB

2,4-Dinitrofluorobenzene

GPCR

G protein-coupled receptor

ICD

Irritant contact dermatitis

IL

Interleukin

Iso

Isoeugenol

KGF

Keratinocyte growth factor

MAPK

Mitogen-activated protein kinase

MβCD

Methyl-β-cyclodextrin

Oxa

Oxazolone

RHE

Reconstructed human epidermis

Supplementary material

403_2012_1209_MOESM1_ESM.pdf (189 kb)
Supplementary material 1 (PDF 189 kb)

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Aurélie Frankart
    • 1
  • Alain Coquette
    • 2
  • Klaus-Rudolf Schroeder
    • 3
  • Yves Poumay
    • 1
  1. 1.Cell and Tissue Laboratory, URPHYM (Research Unit for Molecular Physiology)NARILIS, University of Namur (FUNDP)NamurBelgium
  2. 2.Department of BiologySGS Life ScienceWavreBelgium
  3. 3.Henkel AG & Co.DüsseldorfGermany

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