Cytokine modulation of atopic dermatitis filaggrin skin expression

Michael D. Howell, Byung Eui Kim, Peisong Gao, Audrey V. Grant, Mark Boguniewicz, Anna DeBenedetto, Lynda Schneider, Lisa A. Beck, Kathleen C. Barnes, Donald Y.M. Leung

Research output: Contribution to journalArticle

Abstract

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by a defective skin barrier function. Recent studies have reported mutations of the skin barrier gene encoding filaggrin in a subset of patients with AD. Objective: We investigated whether reduced filaggrin expression was found in patients with AD who were not carriers of known filaggrin mutations and whether filaggrin expression was modulated by the atopic inflammatory response. Methods: Filaggrin expression was measured in skin biopsies and cultured keratinocytes using real-time RT-PCR and immunohistochemistry. Filaggrin loss-of-function mutations were screened in a total of 69 subjects. Results: Compared with normal skin, filaggrin expression was significantly reduced (P < .05) in acute AD skin, with further reduction seen in acute lesions from 3 European American subjects with AD who were heterozygous for the 2282del4 mutation. This was confirmed by using immunohistochemistry. AD skin is characterized by the overexpression of IL-4 and IL-13. Keratinocytes differentiated in the presence of IL-4 and IL-13 exhibited significantly reduced filaggrin gene expression (0.04 ± 0.01 ng filaggrin/ng glyceraldehyde 3-phosphate dehydrogenase; P < .05) compared with media alone (0.16 ± 0.03). Conclusion: Patients with AD have an acquired defect in filaggrin expression that can be modulated by the atopic inflammatory response. Clinical implications: The atopic immune response contributes to the skin barrier defect in AD; therefore, neutralization of IL-4 and IL-13 could improve skin barrier integrity.

Original languageEnglish (US)
Pages (from-to)150-155
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume120
Issue number1
DOIs
StatePublished - Jul 1 2007

Keywords

  • Atopic dermatitis
  • filaggrin
  • skin barrier

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Howell, M. D., Kim, B. E., Gao, P., Grant, A. V., Boguniewicz, M., DeBenedetto, A., Schneider, L., Beck, L. A., Barnes, K. C., & Leung, D. Y. M. (2007). Cytokine modulation of atopic dermatitis filaggrin skin expression. Journal of Allergy and Clinical Immunology, 120(1), 150-155. https://doi.org/10.1016/j.jaci.2007.04.031