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The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis

Inflammasome activation in the innate immune response plays a role in the pathogenesis of psoriasis largely due to the increased levels of pro-inflammatory cytokines. However, the precise role of inflammasomes in psoriasis (Ps) and psoriatic arthritis (PsA) is largely undefined. To establish the rel...

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Autores principales: Forouzandeh, Mahtab, Besen, Jaren, Keane, Robert W., de Rivero Vaccari, Juan Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438850/
https://www.ncbi.nlm.nih.gov/pubmed/32903782
http://dx.doi.org/10.3389/fphar.2020.01238
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author Forouzandeh, Mahtab
Besen, Jaren
Keane, Robert W.
de Rivero Vaccari, Juan Pablo
author_facet Forouzandeh, Mahtab
Besen, Jaren
Keane, Robert W.
de Rivero Vaccari, Juan Pablo
author_sort Forouzandeh, Mahtab
collection PubMed
description Inflammasome activation in the innate immune response plays a role in the pathogenesis of psoriasis largely due to the increased levels of pro-inflammatory cytokines. However, the precise role of inflammasomes in psoriasis (Ps) and psoriatic arthritis (PsA) is largely undefined. To establish the reliability of inflammasome signaling proteins as diagnostics and predictive biomarkers of clinical severity in this disease population, serum from healthy donors and patients with Ps/PsA were analyzed for the protein expression of caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin (IL)-1β and IL-18 levels to determine cut-off points, positive and negative predictive values, and receiver operator characteristic (ROC) curves. Our data revealed that ASC and IL-18 proteins were significantly higher in the Ps group when compared to healthy controls. The area under the curve (AUC) for ASC was 0.9224 with a cut-off point of 321.8 pg/ml, while IL-18 had an AUC of 0.7818 and a cut-off point of 232.1 pg/ml. In addition, levels of IL-18 had a statistically significant linear correlation with that of ASC with an adjusted R squared of 0.2566, indicating that approximately 25% of IL-18 levels could be explained by ASC levels in serum. Our findings indicate that ASC and IL-18 play a significant role in the inflammatory response associated with the pathology of Ps. These inflammasome proteins appear to be key biomarkers in determining diagnoses in this patient population.
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spelling pubmed-74388502020-09-03 The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis Forouzandeh, Mahtab Besen, Jaren Keane, Robert W. de Rivero Vaccari, Juan Pablo Front Pharmacol Pharmacology Inflammasome activation in the innate immune response plays a role in the pathogenesis of psoriasis largely due to the increased levels of pro-inflammatory cytokines. However, the precise role of inflammasomes in psoriasis (Ps) and psoriatic arthritis (PsA) is largely undefined. To establish the reliability of inflammasome signaling proteins as diagnostics and predictive biomarkers of clinical severity in this disease population, serum from healthy donors and patients with Ps/PsA were analyzed for the protein expression of caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin (IL)-1β and IL-18 levels to determine cut-off points, positive and negative predictive values, and receiver operator characteristic (ROC) curves. Our data revealed that ASC and IL-18 proteins were significantly higher in the Ps group when compared to healthy controls. The area under the curve (AUC) for ASC was 0.9224 with a cut-off point of 321.8 pg/ml, while IL-18 had an AUC of 0.7818 and a cut-off point of 232.1 pg/ml. In addition, levels of IL-18 had a statistically significant linear correlation with that of ASC with an adjusted R squared of 0.2566, indicating that approximately 25% of IL-18 levels could be explained by ASC levels in serum. Our findings indicate that ASC and IL-18 play a significant role in the inflammatory response associated with the pathology of Ps. These inflammasome proteins appear to be key biomarkers in determining diagnoses in this patient population. Frontiers Media S.A. 2020-08-11 /pmc/articles/PMC7438850/ /pubmed/32903782 http://dx.doi.org/10.3389/fphar.2020.01238 Text en Copyright © 2020 Forouzandeh, Besen, Keane and de Rivero Vaccari http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Forouzandeh, Mahtab
Besen, Jaren
Keane, Robert W.
de Rivero Vaccari, Juan Pablo
The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis
title The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis
title_full The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis
title_fullStr The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis
title_full_unstemmed The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis
title_short The Inflammasome Signaling Proteins ASC and IL-18 as Biomarkers of Psoriasis
title_sort inflammasome signaling proteins asc and il-18 as biomarkers of psoriasis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438850/
https://www.ncbi.nlm.nih.gov/pubmed/32903782
http://dx.doi.org/10.3389/fphar.2020.01238
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