Transient Receptor Potential Ankyrin 1 (TRPA1)-An Inflammation-Induced Factor in Human HaCaT Keratinocytes

• Published in: International journal of molecular sciences 2021-03, Vol.22 (7), p.3322
• Main Authors: Luostarinen, Samu, Hämäläinen, Mari, Moilanen, Eeva
• Format: Article
• Language: English
• Subjects: Arthritis; Binding sites; c-Jun protein; Calcineurin; Calcineurin inhibitors; Cyclosporins; Cytokines; Dermatitis; Dexamethasone; Drug dosages; Glucocorticoids; Inflammation; JNK protein; Keratinocytes; Kinases; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; NF-κB protein; Physiology; Proteins; Sensory neurons; Skin diseases; Tacrolimus; Therapeutic targets; Transcription factors; transient receptor potential ankyrin 1 (TRPA1) cation channel; Transient receptor potential proteins; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22073322

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 to support inflammatory responses. To address the role of TRPA1 in skin inflammation, we aimed to investigate expression in keratinocytes. HaCaT cells (a model of human keratinocytes) and skin biopses from wild-type and deficient mice were used in the studies. 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 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.