41 S100A8/A9, a Damp Molecule Activated by IL-17 and House Dust Mite is Upregulated in Atopic Dermatitis

BACKGROUND: S100A8/A9 (Calgranulin A/B, Calprotectin), a heterodimer of 2 calcium-binding proteins originally found in the cytoplasm of neutrophils and membrane of monocytes. It has emerged as an important pro-inflammatory mediator, so called “damage-associated molecular pattern (DAMP)” molecule in acute and chronic inflammation. Our previous proteomics data showed that S100A8/A9 was significantly downregulated after immunotherapy with house dust mite in patients with atopic dermatitis (AD). METHODS: The purpose of this study was to evaluate S100A8/A9 expression in serum and lesional skin of AD patients, and then to assess S100A8/A9 expression in HaCaT cells and primary human keratinocytes, which were cultured with Th2, Th17 cytokines and house dust mite (HDM) extracts. RESULTS: Compared with healthy controls, serum S100A8/A9 levels were higher in AD patients and correlated with eczema area and severity index (EASI) scores (P < 0.01, r(2) = 0.2037). S100A8/A9 was strongly expressed in the upper epidermis of AD tissues by immunofluorescence. IL-17A strongly induced S100A8/A9, and enhanced S100A8/A9 expression in HaCaT cells and human keratinocytes which were cultured with Th2 cytokines. S100A8/A9 mRNA and protein levels were also increased in HaCaT cells and human keratinocytes which were stimulated with Dermatophagoides farinae by time dependent manner. IL-17A also strongly enhanced S100A8/A9 expression in HaCaT cells which were cultured with D. farinae, but Th2 cytokines did not. CONCLUSIONS: These results suggest that elevated S100A8/A9 levels of AD patients may reflect the importance of DAMP-associated inflammation, which could be triggered by Th17 cytokines and HDM allergens in AD.