Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes in atopic dermatitis: Implications for sustained dendritic cell activation in the skin

Saveria Pastore, Emanuele Fanales-Belasio, Cristina Albanesi, Luca M. Chinni, Alberto Giannetti, Giampiero Girolomoni

Research output: Contribution to journalArticlepeer-review

Abstract

Lesional skin of atopic dermatitis (AD) harbors high numbers of dendritic cells with enhanced stimulatory capacity for T lymphocytes. In this study, lesional AD skin was shown to stain heavily in both epidermal and dermal compartments for GM-CSF, a cytokine crucial to dendritic cell functions. Keratinocyte cultures established from uninvolved skin of AD patients exhibited markedly increased spontaneous and PMA-stimulated release of GM-CSF compared with keratinocytes from nonatopic controls. Correspondingly, keratinocytes from AD patients showed higher constitutive as well as PMA-induced GM-CSF gene expression. Larger amounts of GM-CSF were produced by AD keratinocytes, also in response to IL-1α, but not after stimulation with LPS, lipoteichoic acid, or staphylococcal enterotoxin B. Hydrocortisone reduced GM-CSF gene expression and protein release in both atopic and control keratinocytes. Supernatants from atopic keratinocytes were able to strongly stimulate PBMC proliferation in a GM-CSF-dependent manner. Moreover, conditioned medium from PMA-treated AD keratinocytes, together with exogenous IL-4, could support phenotypical and functional maturation of peripheral blood precursors into dendritic cells. Enhanced production of GM- CSF by keratinocytes may contribute relevantly to the establishment and chronicity of AD lesions, in particular to the increased number, sustained activation, and enhanced antigen-presenting functions of dendritic cells.

Original languageEnglish
Pages (from-to)3009-3017
Number of pages9
JournalJournal of Clinical Investigation
Volume99
Issue number12
Publication statusPublished - Jun 15 1997

Keywords

  • Antigen-presenting cells
  • Atopic dermatitis
  • Cytokines
  • Epithelium
  • Inflammation

ASJC Scopus subject areas

  • Medicine(all)

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