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.
Highlights
Transient Receptor Potential Ankyrin 1 (TRPA1) is an ion channel localized to the plasma membrane
As TRPA1 seems to have a significant role in models of inflammatory skin conditions such as atopic dermatitis and allergic contact dermatitis, and keratinocytes contribute to the pathogenesis of these skin conditions, we aimed to study TRPA1 expression in human HaCaT keratinocytes exposed to inflammatory stimuli
TRPA1 Expression Is Enhanced by tumor necrosis factor (TNF) in Human HaCaT Keratinocytes
Summary
Transient Receptor Potential Ankyrin 1 (TRPA1) is an ion channel localized to the plasma membrane. It mediates ion currents, mainly Ca2+ and Na+, and other cations such as Zn2+. TRPA1 expression is well characterized in Aδ and C-type fibers, where it functions mediating pain and hyperalgesia [2,3]. TRPA1 expression has been characterized in some nonneuronal cells such as synoviocytes [5] and chondrocytes [6]. In these cells, TRPA1 has been shown to promote inflammatory responses [5,6] but its physiological functions in nonneuronal cells remain unclear
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