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1.
J Invest Dermatol ; 130(5): 1355-64, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20107483

RESUMO

Human skin can defend itself against potentially invading microorganisms by production of antimicrobial peptides (AMPs). The expression of AMPs in atopic dermatitis (AD) is still emerging. To gain more insight into the role of AMPs in AD, we systematically analyzed the expression of ribonuclease 7 (RNase 7), psoriasin, and human beta-defensins (hBD)-2 and -3 in AD compared with psoriatic and healthy control skin as well as after experimental barrier disruption. Immunostaining revealed enhanced expression of all AMPs in the lesional skin of untreated AD and psoriasis when compared with non-lesional skin and controls. Accordingly, induced in vivo secretion of RNase 7, psoriasin, and hBD-2 was detected using ELISA on lesional skin in AD and in even higher concentrations in psoriasis. The secretion of AMPs did not correlate with severity of AD and Staphylococcus aureus colonization. Skin barrier disruption caused enhanced immunoreactivity of hBD-2 and hBD-3 after 24 hours. Strong secretion of RNase 7 was already detected after 1 hour, whereas hBD-2 secretion was significantly enhanced after 24 hours only under occlusion. Thus, a disturbed skin barrier may trigger AMP induction in AD and psoriasis. The functional role of AMP in AD, especially with regard to the control of S. aureus colonization, needs further analysis.


Assuntos
Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Ribonucleases/metabolismo , Proteínas S100/metabolismo , beta-Defensinas/metabolismo , Adolescente , Adulto , Idoso , Peptídeos Catiônicos Antimicrobianos/metabolismo , Biópsia , Criança , Pré-Escolar , Dermatite Atópica/patologia , Epiderme/lesões , Epiderme/metabolismo , Epiderme/patologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Psoríase/metabolismo , Psoríase/patologia , Proteína A7 Ligante de Cálcio S100 , Índice de Gravidade de Doença , Infecções Cutâneas Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/metabolismo , Infecções Cutâneas Estafilocócicas/patologia , Adulto Jovem
2.
Mod Pathol ; 23(4): 511-21, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20098411

RESUMO

During the progression of cutaneous melanomas, matrix metalloproteinases (MMPs) facilitate the tumour cells to traverse the basement membrane and invade the dermis. In this study, we analysed the expression of MMP19 in the course of melanoma progression. Although MMP19 was absent in melanocytes and melanoma cells of early stages of melanoma development, its expression was strongly upregulated in the neighbouring keratinocytes that may facilitate the vertical outgrowth of melanoma cells. In contrast to early stages, MMP19 was upregulated during the vertical growth phase of melanoma and in metastases. The upregulation of MMP19 in melanoma of Clark levels IV and V correlates with that of MMP2 and also simultaneously with ceased expression of E-cadherin. To reveal whether MMP19 facilitates the invasion of melanomas, we examined adhesion and migratory capacity of selected melanoma cell lines. Melanoma cell lines with low expression of MMP19 exhibited increased adhesion to various substrates and lower migration in comparison with the cell line with higher expression of MMP19. Moreover, ectopic expression of MMP19 could restore the migratory capacity of melanoma cells with low endogenous level of MMP19. These results suggest that the increase of MMP19 expression hallmarks the progression of cutaneous melanoma and might augment melanoma growth by promoting the invasion of tumour cells.


Assuntos
Metaloproteinases da Matriz Secretadas/biossíntese , Melanoma/enzimologia , Melanoma/patologia , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/patologia , Western Blotting , Adesão Celular , Movimento Celular , Progressão da Doença , Humanos , Imuno-Histoquímica , Queratinócitos/enzimologia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Regulação para Cima
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