S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3
Autor: | Raquel Navarro, Erwin F. Wagner, Juan Guinea-Viniegra, Ana Guío-Carrión, Helia B. Schonthaler, Isabel Ruppen, Pilar Ximénez-Embún, Keith Ashman, Stefanie K. Wculek, Nancy Hogg |
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Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Proteome
Immunology Inflammation Complement factor I Biology S100A9 S100A8 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Psoriasis medicine Animals Calgranulin B Humans Immunology and Allergy Calgranulin A RNA Small Interfering Promoter Regions Genetic Cells Cultured 030304 developmental biology Cell Nucleus 0303 health sciences Complement C3 medicine.disease 3. Good health Chromatin Disease Models Animal Infectious Diseases Epidermal Cells Gene Expression Regulation 030220 oncology & carcinogenesis Cancer research medicine.symptom Calprotectin Epidermis Protein Binding |
Zdroj: | Immunity |
ISSN: | 1074-7613 |
DOI: | 10.1016/j.immuni.2013.11.011 |
Popis: | SummaryPsoriasis 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. |
Databáze: | OpenAIRE |
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