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J Clin Invest. 1997 Jun 15;99(12):3009-17.

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

Author information

1
Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, 00167 Rome, Italy. pastore@idi.it

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-1alpha, 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.

PMID:
9185525
PMCID:
PMC508153
DOI:
10.1172/JCI119496
[Indexed for MEDLINE]
Free PMC Article

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