S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3.
Immunity
; 39(6): 1171-81, 2013 Dec 12.
Article
em En
| MEDLINE
| ID: mdl-24332034
ABSTRACT
Psoriasis is a common heterogeneous inflammatory skin disease with a complex pathophysiology and limited treatment options. Here we performed proteomic analyses of human psoriatic epidermis and found S100A8-S100A9, also called calprotectin, as the most upregulated proteins, followed by the complement component C3. Both S100A8-S100A9 and C3 are specifically expressed in lesional psoriatic skin. S100A9 is shown here to function as a chromatin component modulating C3 expression in mouse and human cells by binding to a region upstream of the C3 start site. When S100A9 was genetically deleted in mouse models of skin inflammation, the psoriasis-like skin disease and inflammation were strongly attenuated, with a mild immune infiltrate and decreased amounts of C3. In addition, inhibition of C3 in the mouse model strongly reduced the inflammatory skin disease. Thus, S100A8-S100A9 can regulate C3 at the nuclear level and present potential new therapeutic targets for psoriasis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Psoríase
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Complemento C3
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Regulação da Expressão Gênica
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Calgranulina A
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Calgranulina B
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article