Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities
Abstract. Introduction: Epidermal keratinocytes are increasingly recognized as active participants in the sensory transduction of itch and pain, processes known to involve primary afferent glutamatergic neurons. However, the role of keratinocyte glutamate signaling in sensory functioning is not full...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2016-09-01
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| Series: | PAIN Reports |
| Online Access: | http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000000573 |
| _version_ | 1819034289430331392 |
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| author | David Cabañero Takeshi Irie Marta Celorrio Christopher Trousdale David M. Owens David Virley Phillip J. Albrecht Michael J. Caterina Frank L. Rice Jose A. Morón |
| author_facet | David Cabañero Takeshi Irie Marta Celorrio Christopher Trousdale David M. Owens David Virley Phillip J. Albrecht Michael J. Caterina Frank L. Rice Jose A. Morón |
| author_sort | David Cabañero |
| collection | DOAJ |
| description | Abstract. Introduction: Epidermal keratinocytes are increasingly recognized as active participants in the sensory transduction of itch and pain, processes known to involve primary afferent glutamatergic neurons. However, the role of keratinocyte glutamate signaling in sensory functioning is not fully understood. Here, we present the observation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid–type glutamate receptors (AMPARs) in epidermal keratinocytes.
Methods: Immunohistochemical and in situ hybridization analyses were conducted to assess the expression of AMPAR subunits in epidermal keratinocytes in mouse and human skin samples, and in organotypic cultures of human keratinocytes. In addition, reverse transcription PCR further confirmed the expression of GluA4-containing AMPAR in epidermal keratinocytes.
Results: We found prominent immunolabeling for the GluA4 subunit of AMPAR in keratinocytes of glabrous and hairy skin of mouse epidermis, as well as in human epidermal keratinocytes. Reverse transcription PCR confirmed Gria4 transcript expression in epidermal mouse keratinocytes. In addition, expression of GRIA4 mRNA was confirmed in epidermal human keratinocytes by in situ hybridization. Immunohistochemical studies conducted in human skin biopsies from patients with atopic dermatitis and postherpetic neuralgia demonstrate that keratinocyte expression of GluA4 can be altered under pathological conditions. Moreover, a decrease of GluA4 expression was observed in organotypic cultures of human keratinocytes after direct application of algogenic agents.
Conclusion: We provide evidence that GluA4-containing AMPARs are expressed in epidermal keratinocytes, that human pruritic and painful dermatopathologies have alterations in the keratinocyte expression levels of GluA4-containing AMPAR, and that itch- and pain-producing substances can directly regulate their production in keratinocytes. |
| first_indexed | 2024-12-21T07:31:22Z |
| format | Article |
| id | doaj.art-e152b694ec644dbe9c9a63450a7b074c |
| institution | Directory Open Access Journal |
| issn | 2471-2531 |
| language | English |
| last_indexed | 2024-12-21T07:31:22Z |
| publishDate | 2016-09-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | PAIN Reports |
| spelling | doaj.art-e152b694ec644dbe9c9a63450a7b074c2022-12-21T19:11:34ZengWolters KluwerPAIN Reports2471-25312016-09-0113e57310.1097/PR9.0000000000000573201609000-00005Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalitiesDavid Cabañero0Takeshi Irie1Marta Celorrio2Christopher Trousdale3David M. Owens4David Virley5Phillip J. Albrecht6Michael J. Caterina7Frank L. Rice8Jose A. Morón9aDepartment of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St Louis, MO, USAcDepartment of Anesthesiology and Critical Care, Memorial Sloan Kettering Cancer Center, New York, NY, USAaDepartment of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St Louis, MO, USAaDepartment of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St Louis, MO, USAdDepartment of Dermatology, Columbia University Medical Center, New York, NY, USAfTranspharmation Ltd, London Bioscience Innovation Centre, London, United KingdomgIntegrated Tissue Dynamics, Rensselaer, NY, USAhDepartment of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD, USAgIntegrated Tissue Dynamics, Rensselaer, NY, USAaDepartment of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St Louis, MO, USAAbstract. Introduction: Epidermal keratinocytes are increasingly recognized as active participants in the sensory transduction of itch and pain, processes known to involve primary afferent glutamatergic neurons. However, the role of keratinocyte glutamate signaling in sensory functioning is not fully understood. Here, we present the observation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid–type glutamate receptors (AMPARs) in epidermal keratinocytes. Methods: Immunohistochemical and in situ hybridization analyses were conducted to assess the expression of AMPAR subunits in epidermal keratinocytes in mouse and human skin samples, and in organotypic cultures of human keratinocytes. In addition, reverse transcription PCR further confirmed the expression of GluA4-containing AMPAR in epidermal keratinocytes. Results: We found prominent immunolabeling for the GluA4 subunit of AMPAR in keratinocytes of glabrous and hairy skin of mouse epidermis, as well as in human epidermal keratinocytes. Reverse transcription PCR confirmed Gria4 transcript expression in epidermal mouse keratinocytes. In addition, expression of GRIA4 mRNA was confirmed in epidermal human keratinocytes by in situ hybridization. Immunohistochemical studies conducted in human skin biopsies from patients with atopic dermatitis and postherpetic neuralgia demonstrate that keratinocyte expression of GluA4 can be altered under pathological conditions. Moreover, a decrease of GluA4 expression was observed in organotypic cultures of human keratinocytes after direct application of algogenic agents. Conclusion: We provide evidence that GluA4-containing AMPARs are expressed in epidermal keratinocytes, that human pruritic and painful dermatopathologies have alterations in the keratinocyte expression levels of GluA4-containing AMPAR, and that itch- and pain-producing substances can directly regulate their production in keratinocytes.http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000000573 |
| spellingShingle | David Cabañero Takeshi Irie Marta Celorrio Christopher Trousdale David M. Owens David Virley Phillip J. Albrecht Michael J. Caterina Frank L. Rice Jose A. Morón Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities PAIN Reports |
| title | Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities |
| title_full | Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities |
| title_fullStr | Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities |
| title_full_unstemmed | Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities |
| title_short | Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities |
| title_sort | identification of an epidermal keratinocyte ampa glutamate receptor involved in dermatopathies associated with sensory abnormalities |
| url | http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000000573 |
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