title: Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes in atopic dermatitis. Implications for sustained dendritic cell activation in the skin.
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.
authors.affiliation: Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, 00167 Rome, Italy. pastore@idi.it
authors.forename: S
authors.initials: S
authors.lastname: Pastore
authors.forename: E
authors.initials: E
authors.lastname: Fanales-Belasio
authors.forename: C
authors.initials: C
authors.lastname: Albanesi
authors.forename: L M
authors.initials: LM
authors.lastname: Chinni
authors.forename: A
authors.initials: A
authors.lastname: Giannetti
authors.forename: G
authors.initials: G
authors.lastname: Girolomoni
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003876:Dermatitis, Atopic / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D007375:Interleukin-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone