DAMP molecules S100A9 and S100A8 activated by IL-17A and house-dust mites are increased in atopic dermatitis

Exp Dermatol. 2014 Dec;23(12):938-41. doi: 10.1111/exd.12563.

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.

Keywords: Dermatophagoides farinae; IL-17A; IL-33; S100A8; S100A9; atopic dermatitis.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calgranulin A / metabolism*
  • Calgranulin B / metabolism*
  • Cell Line
  • Cytokines / metabolism
  • Dermatitis, Atopic / etiology
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / immunology*
  • Dermatophagoides farinae / immunology*
  • Dermatophagoides farinae / pathogenicity
  • Humans
  • Immunity, Innate
  • Interleukin-17 / metabolism*
  • Interleukin-33
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Keratinocytes / immunology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Th17 Cells / immunology
  • Th2 Cells / immunology
  • Up-Regulation

Substances

  • Calgranulin A
  • Calgranulin B
  • Cytokines
  • IL17A protein, human
  • IL33 protein, human
  • Interleukin-17
  • Interleukin-33
  • Interleukins
  • RNA, Messenger