Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases
We previously showed that genotoxic stress induced an active extracellular release of nucleophosmin (NPM) in human cardiac mesenchymal progenitor cells, and that serum deprivation provokes NPM secretion from human endothelial cells, eliciting inflammation via nuclear factor kappa B (NF-kB) transcrip...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.867813/full |
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| author | Marco D'Agostino Sara Beji Sara Sileno Daniela Lulli Laura Mercurio Stefania Madonna Corrado Cirielli Sabatino Pallotta Cristina Albanesi Maurizio C. Capogrossi Maurizio C. Capogrossi Daniele Avitabile Guido Melillo Alessandra Magenta |
| author_facet | Marco D'Agostino Sara Beji Sara Sileno Daniela Lulli Laura Mercurio Stefania Madonna Corrado Cirielli Sabatino Pallotta Cristina Albanesi Maurizio C. Capogrossi Maurizio C. Capogrossi Daniele Avitabile Guido Melillo Alessandra Magenta |
| author_sort | Marco D'Agostino |
| collection | DOAJ |
| description | We previously showed that genotoxic stress induced an active extracellular release of nucleophosmin (NPM) in human cardiac mesenchymal progenitor cells, and that serum deprivation provokes NPM secretion from human endothelial cells, eliciting inflammation via nuclear factor kappa B (NF-kB) transcriptional activation. In this study, we wanted to determine whether NPM was similarly modulated in the skin and plasma of psoriatic patients (Pso). We found that NPM was induced in 6 skin biopsies compared to 6 normal skin biopsies and was markedly increased in lesional (LS) vs. non-lesional skin (NLS) biopsies. Moreover, NPM was also increased at the transcriptional levels in LS vs. NLS. Both the innate stimuli, such as lipopolysaccharides and Poly inositol–cytosine and adaptive stimuli, that is, cytokine mix, were able to induce the extracellular release of NPM in immortalized keratinocytes and human skin fibroblasts in the absence of cytotoxicity. Interestingly, NPM interacts with Toll-like receptor (TLR)4 in these cells and activates an NF-kB-dependent inflammatory pathway upregulating interleukin IL-6 and COX-2 gene expression. Finally, circulating NPM was increased in the plasma of 29 Pso compared to 29 healthy controls, and positively correlates with psoriasis area severity index (PASI) and with determinants of cardiovascular diseases (CVDs), such as pulse wave velocity, systolic pressure, and left ventricular mass. Furthermore, NPM positively correlates with miR-200c circulating levels, which we previously showed to increase in Pso and correlate with CVD progression. Our data show that circulating miR-200c is physically associated with extracellular NPM, which most probably is responsible for its extracellular release and protection upon cytokine mix via a TLR4-mechanism. In conclusion, NPM is increased in psoriasis both in the skin and plasma and might be considered a novel biologic target to counteract chronic inflammation associated with CVD risk. |
| first_indexed | 2024-04-13T07:48:19Z |
| format | Article |
| id | doaj.art-a4435b80c7ac44879675ecec33467ac9 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-13T07:48:19Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-a4435b80c7ac44879675ecec33467ac92022-12-22T02:55:37ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-04-01910.3389/fcvm.2022.867813867813Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular DiseasesMarco D'Agostino0Sara Beji1Sara Sileno2Daniela Lulli3Laura Mercurio4Stefania Madonna5Corrado Cirielli6Sabatino Pallotta7Cristina Albanesi8Maurizio C. Capogrossi9Maurizio C. Capogrossi10Daniele Avitabile11Guido Melillo12Alessandra Magenta13Experimental Immunology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, ItalyExperimental Immunology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, ItalyNational Research Council of Italy (CNR), Institute of Translational Pharmacology (IFT), Rome, ItalyExperimental Immunology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, ItalyExperimental Immunology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, ItalyExperimental Immunology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, ItalyUnit of Vascular Surgery, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, ItalyDivision of Dermatology, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, ItalyExperimental Immunology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, ItalyDivision of Cardiology, Johns Hopkins Bayview Medical Center, Johns Hopkins University, Baltimore, MD, United StatesLaboratory of Cardiovascular Science, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, United StatesIdi Farmaceutici S.r.l., Pomezia, ItalyUnit of Cardiology, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, ItalyNational Research Council of Italy (CNR), Institute of Translational Pharmacology (IFT), Rome, ItalyWe previously showed that genotoxic stress induced an active extracellular release of nucleophosmin (NPM) in human cardiac mesenchymal progenitor cells, and that serum deprivation provokes NPM secretion from human endothelial cells, eliciting inflammation via nuclear factor kappa B (NF-kB) transcriptional activation. In this study, we wanted to determine whether NPM was similarly modulated in the skin and plasma of psoriatic patients (Pso). We found that NPM was induced in 6 skin biopsies compared to 6 normal skin biopsies and was markedly increased in lesional (LS) vs. non-lesional skin (NLS) biopsies. Moreover, NPM was also increased at the transcriptional levels in LS vs. NLS. Both the innate stimuli, such as lipopolysaccharides and Poly inositol–cytosine and adaptive stimuli, that is, cytokine mix, were able to induce the extracellular release of NPM in immortalized keratinocytes and human skin fibroblasts in the absence of cytotoxicity. Interestingly, NPM interacts with Toll-like receptor (TLR)4 in these cells and activates an NF-kB-dependent inflammatory pathway upregulating interleukin IL-6 and COX-2 gene expression. Finally, circulating NPM was increased in the plasma of 29 Pso compared to 29 healthy controls, and positively correlates with psoriasis area severity index (PASI) and with determinants of cardiovascular diseases (CVDs), such as pulse wave velocity, systolic pressure, and left ventricular mass. Furthermore, NPM positively correlates with miR-200c circulating levels, which we previously showed to increase in Pso and correlate with CVD progression. Our data show that circulating miR-200c is physically associated with extracellular NPM, which most probably is responsible for its extracellular release and protection upon cytokine mix via a TLR4-mechanism. In conclusion, NPM is increased in psoriasis both in the skin and plasma and might be considered a novel biologic target to counteract chronic inflammation associated with CVD risk.https://www.frontiersin.org/articles/10.3389/fcvm.2022.867813/fullalarmininflammationmicroRNAspsoriasisatherosclerosiscardiovascular diseases |
| spellingShingle | Marco D'Agostino Sara Beji Sara Sileno Daniela Lulli Laura Mercurio Stefania Madonna Corrado Cirielli Sabatino Pallotta Cristina Albanesi Maurizio C. Capogrossi Maurizio C. Capogrossi Daniele Avitabile Guido Melillo Alessandra Magenta Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases Frontiers in Cardiovascular Medicine alarmin inflammation microRNAs psoriasis atherosclerosis cardiovascular diseases |
| title | Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases |
| title_full | Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases |
| title_fullStr | Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases |
| title_full_unstemmed | Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases |
| title_short | Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases |
| title_sort | extracellular nucleophosmin is increased in psoriasis and correlates with the determinants of cardiovascular diseases |
| topic | alarmin inflammation microRNAs psoriasis atherosclerosis cardiovascular diseases |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.867813/full |
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