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DAMP molecules S100A9 and S100A8 activated by IL-17A and house-dust mites are increased in atopic dermatitis
Shan Jin1, Chang Ook Park, Jung U Shin
1Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea; Department of Dermatology, Yanbian University Hospital, Yanji, Jilin, China.
Abstract:
S100A9 and S100A8 are called damage-associated molecular pattern (DAMP) molecules because of their pro-inflammatory properties. Few studies have evaluated S100A9 and S100A8 function as DAMP molecules in atopic dermatitis (AD). We investigated how house-dust mites affect S100A9 and S100A8 expression in Th2 cytokine- and Th17 cytokine-treated keratinocytes, and how secretion of these molecules affects keratinocyte-derived cytokines. Finally, we evaluated expression of these DAMP molecules in AD patients. S100A9 expression and S100A8 expression were strongly induced in IL-17A- and Dermatophagoides (D.) farinae-treated keratinocytes, respectively. Furthermore, co-treatment with D. farinae and IL-17A strongly increased expression of S100A9 and S100A8 compared with D. farinae-Th2 cytokine co-treatment. The IL-33 mRNA level increased in a dose-dependent manner in S100A9-treated keratinocytes, but TSLP expression did not change. S100A8/A9 levels were also higher in the lesional skin and serum of AD patients, and correlated with disease severity. Taken together, S100A9 and S100A8 may be involved in inducing DAMP-mediated inflammation in AD triggered by IL-17A and house-dust mites.
Insights
Damage-associated molecular pattern (DAMP) molecules S100A9 and S100A8 are elevated in atopic dermatitis (AD). IL-17A and house dust mites significantly increase their expression, suggesting a role in AD pathogenesis.
Area of Science:
- Immunology
- Dermatology
- Molecular Biology
Background:
- S100A9 and S100A8 are pro-inflammatory damage-associated molecular pattern (DAMP) molecules.
- Their role as DAMPs in atopic dermatitis (AD) requires further investigation.
Discussion:
- House dust mite (Dermatophagoides farinae) and IL-17A synergistically induce S100A9 and S100A8 expression in keratinocytes.
- S100A9 treatment dose-dependently increases IL-33 mRNA levels in keratinocytes.
- S100A8/A9 levels correlate with disease severity in AD patients' skin and serum.
Key Insights:
- S100A9 and S100A8 are significantly upregulated in AD.
- IL-17A and house dust mite exposure are key drivers of S100A9/S100A8 induction in AD.
- These DAMPs may contribute to IL-33-mediated inflammation in AD.
Outlook:
- Further research into S100A9/S100A8 as therapeutic targets in AD.
- Investigating the precise mechanisms of S100A9/S100A8 in keratinocyte-cytokine crosstalk.
- Exploring the role of IL-17A in exacerbating AD through S100A9/S100A8 induction.
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