Subject(s)
Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/immunology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Skin Neoplasms/enzymology , Skin Neoplasms/immunology , Adult , Aged , Carcinoma, Squamous Cell/etiology , Female , Humans , Immune Tolerance , Immunocompetence , Male , Middle Aged , Skin/enzymology , Skin Neoplasms/etiologyABSTRACT
BACKGROUND: Cytokines are of potential importance in the pathogenesis of cutaneous T-cell mediated disorders, including cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To compare interleukin (IL)-15 expression in certain inflammatory cutaneous diseases, with that in CTCL (mycosis fungoides and Sézary syndrome). METHODS: IL-15 mRNA and protein expression were examined by in situ hybridization and immunohistochemistry, respectively, on formalin-fixed, paraffin-embedded biopsies of normal human skin, atopic dermatitis, psoriasis, parapsoriasis and CTCL. RESULTS: Despite similar expression of IL-15 mRNA, we found differences in IL-15 protein expression between normal human skin, atopic dermatitis and psoriasis on the one hand, and parapsoriasis and CTCL on the other. IL-15 protein expression was not detected in normal human skin, atopic dermatitis or psoriasis, but was detected, mainly at low levels but in a few patients at higher levels, in epidermal keratinocytes in parapsoriasis, mycosis fungoides and Sézary syndrome. CONCLUSIONS: Induction of keratinocyte IL-15 expression appears to be a feature of CTCL. The factors stimulating such an expression remain unknown.
Subject(s)
Interleukin-15/metabolism , Mycosis Fungoides/immunology , Sezary Syndrome/immunology , Skin Neoplasms/immunology , Antineoplastic Agents/therapeutic use , Dermatitis, Atopic/immunology , Dermatitis, Atopic/therapy , Gene Expression , Humans , Immunoenzyme Techniques , In Situ Hybridization , Interferon-alpha/therapeutic use , Interleukin-15/genetics , Mycosis Fungoides/therapy , Parapsoriasis/immunology , RNA, Messenger/genetics , Sezary Syndrome/therapy , Skin/immunology , Skin Neoplasms/therapyABSTRACT
The migration of keratinocytes plays an important role in the re-epithelialization of cutaneous wounds. Zinc, copper and manganese are used in vivo for their healing properties and their mechanism of action is still only partially known. Thus, they have been shown both to promote keratinocyte proliferation and to modulate integrins expression. The aim of this study was to determine if trace elements induce an increase of the migration of keratinocytes and if this effect is related to the modulation of integrins. Two independent migration assays were used to study keratinocyte migration: the scratch assay using normal human keratinocytes and the modified Boyden chamber using HaCaT cells. Inhibition studies using function-blocking antibodies directed to alpha3, alpha6, alpha(v) and beta1 subunits were performed to investigate the modulator effect of trace elements on integrin function. In this way, zinc and copper gluconates increased alpha3, alpha(v) and beta1 function whereas manganese gluconate seems mainly able to modulate the function of alpha3 and beta1. The stimulating effect of these trace elements on keratinocyte migration does not appear related to alpha6 subunit. Thus, zinc, copper and manganese enhanced keratinocyte migration and one of the mechanisms was going through a modulation of integrin functions.
