Transient receptor potential ankyrin 1 (Trpa1): an inflammation-induced factor in human hacat keratinocytes

Samu Luostarinen, Mari Hämäläinen, Eeva Moilanen

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Abstract

Transient receptor potential ankyrin 1 (TRPA1) is an ion channel mainly studied in sensory neurons where it mediates itch, pain and neurogenic inflammation. Recently, some nonneuronal cells have also been shown to express TRPA1 to support inflammatory responses. To address the role of TRPA1 in skin inflammation, we aimed to investigate TRPA1 expression in keratinocytes. HaCaT cells (a model of human keratinocytes) and skin biopses from wild-type and TRPA1 deficient mice were used in the studies. TRPA1 expression in nonstimulated keratinocytes was very low but significantly inducible by the proinflammatory cytokine tumor necrosis factor (TNF) in an nuclear factor kappa B (NF-κB), and mitogen-activated protein (MAP) kinase (p38 and c-Jun N-terminal kinase, JNK)-dependent manner. Interestingly, drugs widely used to treat skin inflammation, the calcineurin inhibitors tacrolimus and cyclosporine and the glucocorticoid dexamethasone, significantly decreased TRPA1 expression. Furthermore, pharmacological inhibition and genetic deletion of TRPA1 reduced the synthesis of TNF-induced monocyte chemoattractant protein 1 (MCP-1) in keratinocytes and mouse skin biopsies. In conclusion, these findings point to an inflammatory role for TRPA1 in keratinocytes and present TRPA1 as a potential drug target in inflammatory skin diseases.

Original languageEnglish
Article number3322
JournalInternational Journal of Molecular Sciences
Volume22
Issue number7
DOIs
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed

Keywords

  • Calcineurin inhibitors
  • Glucocorticoids
  • Inflammation
  • Transient receptor potential ankyrin 1 (TRPA1) cation channel
  • Tumor necrosis factor (TNF)

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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