Transient Receptor Potential Ankyrin 1 (TRPA1)—An Inflammation-Induced Factor in Human HaCaT Keratinocytes
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 <i>TRPA1</i> to support inflammatory responses. To address the rol...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3322 |
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| author | Samu Luostarinen Mari Hämäläinen Eeva Moilanen |
| author_facet | Samu Luostarinen Mari Hämäläinen Eeva Moilanen |
| author_sort | Samu Luostarinen |
| collection | DOAJ |
| description | 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 <i>TRPA1</i> to support inflammatory responses. To address the role of TRPA1 in skin inflammation, we aimed to investigate <i>TRPA1</i> expression in keratinocytes. HaCaT cells (a model of human keratinocytes) and skin biopses from wild-type and <i>TRPA1</i> deficient mice were used in the studies. <i>TRPA1</i> 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 <i>TRPA1</i> 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. |
| first_indexed | 2024-03-10T12:56:53Z |
| format | Article |
| id | doaj.art-30bc868907774043abdc8b0e6f5ad5f3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:56:53Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-30bc868907774043abdc8b0e6f5ad5f32023-11-21T11:50:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227332210.3390/ijms22073322Transient Receptor Potential Ankyrin 1 (TRPA1)—An Inflammation-Induced Factor in Human HaCaT KeratinocytesSamu Luostarinen0Mari Hämäläinen1Eeva Moilanen2The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33014 Tampere, FinlandThe Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33014 Tampere, FinlandThe Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33014 Tampere, FinlandTransient 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 <i>TRPA1</i> to support inflammatory responses. To address the role of TRPA1 in skin inflammation, we aimed to investigate <i>TRPA1</i> expression in keratinocytes. HaCaT cells (a model of human keratinocytes) and skin biopses from wild-type and <i>TRPA1</i> deficient mice were used in the studies. <i>TRPA1</i> 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 <i>TRPA1</i> 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.https://www.mdpi.com/1422-0067/22/7/3322transient receptor potential ankyrin 1 (TRPA1) cation channelinflammationtumor necrosis factor (TNF)calcineurin inhibitorsglucocorticoids |
| spellingShingle | Samu Luostarinen Mari Hämäläinen Eeva Moilanen Transient Receptor Potential Ankyrin 1 (TRPA1)—An Inflammation-Induced Factor in Human HaCaT Keratinocytes International Journal of Molecular Sciences transient receptor potential ankyrin 1 (TRPA1) cation channel inflammation tumor necrosis factor (TNF) calcineurin inhibitors glucocorticoids |
| title | Transient Receptor Potential Ankyrin 1 (TRPA1)—An Inflammation-Induced Factor in Human HaCaT Keratinocytes |
| title_full | Transient Receptor Potential Ankyrin 1 (TRPA1)—An Inflammation-Induced Factor in Human HaCaT Keratinocytes |
| title_fullStr | Transient Receptor Potential Ankyrin 1 (TRPA1)—An Inflammation-Induced Factor in Human HaCaT Keratinocytes |
| title_full_unstemmed | Transient Receptor Potential Ankyrin 1 (TRPA1)—An Inflammation-Induced Factor in Human HaCaT Keratinocytes |
| title_short | Transient Receptor Potential Ankyrin 1 (TRPA1)—An Inflammation-Induced Factor in Human HaCaT Keratinocytes |
| title_sort | transient receptor potential ankyrin 1 trpa1 an inflammation induced factor in human hacat keratinocytes |
| topic | transient receptor potential ankyrin 1 (TRPA1) cation channel inflammation tumor necrosis factor (TNF) calcineurin inhibitors glucocorticoids |
| url | https://www.mdpi.com/1422-0067/22/7/3322 |
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