Recombinant S100a7 protein (human, aa 1-101,>95%) [His]

Psoriatic keratinocytes express exaggerated levels of inflammatory cytokines, and show aberrant hyperproliferation and terminal differentiation in the pathogenesis of psoriasis. The antimicrobial protein hS100A7 (psoriasin) has been found highly expressed in psoriatic skin, but the mechanism and physiological function remain largely unknown. We observed that hS100A7 induces mature interleukin 1 alpha (17kDa) expression in normal human epidermal keratinocytes, which is dependent on RAGE-p38 MAPK and calpain-1 as the inhibitors or knockdown of them completely decreased the expression of mature interleukin1 alpha. Then, we proved mS100a7a15, mature IL-1 alpha and calpain-1 were highly expressed in imquimod-induced psoriasis model and mouse IL-17a-neutralizing antibody treatment attenuated mS100a7a15 expression. At last, PD 151746 (calpain-1 inhibitor) treatment decreased epidermal thickness in imquimod-induced psoriasis model. Taken together, our results suggest that mature IL-1 alpha induced by hS100A7 is via RAGE-p38 MAPK and calpain-1 pathway in keratinocyte and this mechanism may play an important role during psoriasis.

Psoriasin (S100A7) is one of the members in the S100 protein family. It was first discovered as a protein abundantly expressed in psoriatic keratinocytes. Psoriasin has been implicated in a wide range of intracellular and extracellular functions, including regulation of calcium homeostasis, cell proliferation, differentiation, apoptosis, cell invasion and motility, cytoskeleton dynamics, protein phosphorylation, regulation of transcriptional factors, immune responses, chemotaxis, inflammation and pluripotency. Altered expression of psoriasin was shown to associate with a broad range of diseases, including inflammatory and immune disorders and tumors. Many lines of evidence suggested that psoriasin exerts its distinct functions through alterations in both intracellular and extracellular pathways and results alteration in gene expression. In this review, we summarize the multiple function of psoriasin and the underlying mechanisms and discuss the potential role of psoriasin as one of the biomarkers and therapeutic targets for multiple diseases.