S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3 - PubMed (original) (raw)

S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3

Helia B Schonthaler et al. Immunity. 2013.

Free article

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.

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Comment in

• [Journal club].
  Rupec RA. Rupec RA. J Dtsch Dermatol Ges. 2014 May;12(5):441. doi: 10.1111/ddg.12350. J Dtsch Dermatol Ges. 2014. PMID: 24797758 German. No abstract available.

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