CARD14 Expression in Dermal Endothelial Cells in Psoriasis
Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead t...
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Public Library of Science
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219711/ |
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pubmed-4219711 |
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pubmed-42197112014-11-12 CARD14 Expression in Dermal Endothelial Cells in Psoriasis Harden, Jamie L. Lewis, Steven M. Pierson, Katherine C. Suárez-Fariñas, Mayte Lentini, Tim Ortenzio, Francesca S. Zaba, Lisa C. Goldbach-Mansky, Raphaela Bowcock, Anne M. Lowes, Michelle A. Research Article Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead to enhanced NF-κB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but also in unidentified dermal cells. In this manuscript, the identity of the dermal cell types expressing CARD14, as well the potential functional consequence of overactive CARD14 in these dermal cell types, was determined. Using two-color immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31+ endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells, such as aortic endothelial cells, which may indicate a role of CARD14+ECs in the systemic inflammation and cardiovascular comorbidities associated with psoriasis. Additionally, phosphorylated NF-κB was found in psoriatic CARD14+ CD31+ ECs, demonstrating this pathway is active in dermal ECs in psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations resulted in increased expression of several chemokines, including CXCL10, IL-8, and CCL2. These results provide preliminary evidence that CARD14 expression in ECs may contribute to psoriasis through increased expression of chemokines and facilitating recruitment of immune cells into skin. Public Library of Science 2014-11-04 /pmc/articles/PMC4219711/ /pubmed/25369198 http://dx.doi.org/10.1371/journal.pone.0111255 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Harden, Jamie L. Lewis, Steven M. Pierson, Katherine C. Suárez-Fariñas, Mayte Lentini, Tim Ortenzio, Francesca S. Zaba, Lisa C. Goldbach-Mansky, Raphaela Bowcock, Anne M. Lowes, Michelle A. |
| spellingShingle |
Harden, Jamie L. Lewis, Steven M. Pierson, Katherine C. Suárez-Fariñas, Mayte Lentini, Tim Ortenzio, Francesca S. Zaba, Lisa C. Goldbach-Mansky, Raphaela Bowcock, Anne M. Lowes, Michelle A. CARD14 Expression in Dermal Endothelial Cells in Psoriasis |
| author_facet |
Harden, Jamie L. Lewis, Steven M. Pierson, Katherine C. Suárez-Fariñas, Mayte Lentini, Tim Ortenzio, Francesca S. Zaba, Lisa C. Goldbach-Mansky, Raphaela Bowcock, Anne M. Lowes, Michelle A. |
| author_sort |
Harden, Jamie L. |
| title |
CARD14 Expression in Dermal Endothelial Cells in Psoriasis |
| title_short |
CARD14 Expression in Dermal Endothelial Cells in Psoriasis |
| title_full |
CARD14 Expression in Dermal Endothelial Cells in Psoriasis |
| title_fullStr |
CARD14 Expression in Dermal Endothelial Cells in Psoriasis |
| title_full_unstemmed |
CARD14 Expression in Dermal Endothelial Cells in Psoriasis |
| title_sort |
card14 expression in dermal endothelial cells in psoriasis |
| description |
Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead to enhanced NF-κB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but also in unidentified dermal cells. In this manuscript, the identity of the dermal cell types expressing CARD14, as well the potential functional consequence of overactive CARD14 in these dermal cell types, was determined. Using two-color immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31+ endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells, such as aortic endothelial cells, which may indicate a role of CARD14+ECs in the systemic inflammation and cardiovascular comorbidities associated with psoriasis. Additionally, phosphorylated NF-κB was found in psoriatic CARD14+ CD31+ ECs, demonstrating this pathway is active in dermal ECs in psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations resulted in increased expression of several chemokines, including CXCL10, IL-8, and CCL2. These results provide preliminary evidence that CARD14 expression in ECs may contribute to psoriasis through increased expression of chemokines and facilitating recruitment of immune cells into skin. |
| publisher |
Public Library of Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219711/ |
| _version_ |
1613152068564942848 |