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

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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.

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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

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Acknowledgments

Technical help from D. Van Vlaender, F. Herphelin and V. De Glas is gratefully acknowledged. Contract grant sponsor was Henkel AG & CoKGaA, FNRS 1.5.033.06F and FRFC 2.4.522.10F.

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The authors have no conflict of interest to declare.

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Correspondence to Yves Poumay.

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Frankart, A., Coquette, A., Schroeder, KR. et al. Studies of cell signaling in a reconstructed human epidermis exposed to sensitizers: IL-8 synthesis and release depend on EGFR activation. Arch Dermatol Res 304, 289–303 (2012). https://doi.org/10.1007/s00403-012-1209-5

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  • DOI: https://doi.org/10.1007/s00403-012-1209-5

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