IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis

Abstract Chronic inflammation is a critical component of atherogenesis, however, reliable human translational models aimed at characterizing these mechanisms are lacking. Psoriasis, a chronic inflammatory skin disease associated with increased susceptibility to atherosclerosis, provides a clinical h...

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Autores principales:	Nehal N. Mehta, Heather L. Teague, William R. Swindell, Yvonne Baumer, Nicole L. Ward, Xianying Xing, Brooke Baugous, Andrew Johnston, Aditya A. Joshi, Joanna Silverman, Drew H. Barnes, Liza Wolterink, Rajan P. Nair, Philip E. Stuart, Martin Playford, John J. Voorhees, Mrinal K. Sarkar, James T. Elder, Katherine Gallagher, Santhi K. Ganesh, Johann E. Gudjonsson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2fc891577ed8496cab73a2b9d95b1c7b
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spelling	oai:doaj.org-article:2fc891577ed8496cab73a2b9d95b1c7b2021-12-02T15:06:02ZIFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis10.1038/s41598-017-14365-12045-2322https://doaj.org/article/2fc891577ed8496cab73a2b9d95b1c7b2017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-14365-1https://doaj.org/toc/2045-2322Abstract Chronic inflammation is a critical component of atherogenesis, however, reliable human translational models aimed at characterizing these mechanisms are lacking. Psoriasis, a chronic inflammatory skin disease associated with increased susceptibility to atherosclerosis, provides a clinical human model that can be utilized to investigate the links between chronic inflammation and atherosclerosis development. We sought to investigate key biological processes in psoriasis skin and human vascular tissue to identify biological components that may promote atherosclerosis in chronic inflammatory conditions. Using a bioinformatics approach of human skin and vascular tissue, we determined IFN-γ and TNF-α are the dominant pro-inflammatory signals linking atherosclerosis and psoriasis. We then stimulated primary aortic endothelial cells and ex-vivo atherosclerotic tissue with IFN-γ and TNF-α and found they synergistically increased monocyte and T-cell chemoattractants, expression of adhesion molecules on the endothelial cell surface, and decreased endothelial barrier integrity in vitro, therefore increasing permeability. Our data provide strong evidence of synergism between IFN-γ and TNF- α in inflammatory atherogenesis and provide rationale for dual cytokine antagonism in future studies.Nehal N. MehtaHeather L. TeagueWilliam R. SwindellYvonne BaumerNicole L. WardXianying XingBrooke BaugousAndrew JohnstonAditya A. JoshiJoanna SilvermanDrew H. BarnesLiza WolterinkRajan P. NairPhilip E. StuartMartin PlayfordJohn J. VoorheesMrinal K. SarkarJames T. ElderKatherine GallagherSanthi K. GaneshJohann E. GudjonssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nehal N. Mehta Heather L. Teague William R. Swindell Yvonne Baumer Nicole L. Ward Xianying Xing Brooke Baugous Andrew Johnston Aditya A. Joshi Joanna Silverman Drew H. Barnes Liza Wolterink Rajan P. Nair Philip E. Stuart Martin Playford John J. Voorhees Mrinal K. Sarkar James T. Elder Katherine Gallagher Santhi K. Ganesh Johann E. Gudjonsson IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis
description	Abstract Chronic inflammation is a critical component of atherogenesis, however, reliable human translational models aimed at characterizing these mechanisms are lacking. Psoriasis, a chronic inflammatory skin disease associated with increased susceptibility to atherosclerosis, provides a clinical human model that can be utilized to investigate the links between chronic inflammation and atherosclerosis development. We sought to investigate key biological processes in psoriasis skin and human vascular tissue to identify biological components that may promote atherosclerosis in chronic inflammatory conditions. Using a bioinformatics approach of human skin and vascular tissue, we determined IFN-γ and TNF-α are the dominant pro-inflammatory signals linking atherosclerosis and psoriasis. We then stimulated primary aortic endothelial cells and ex-vivo atherosclerotic tissue with IFN-γ and TNF-α and found they synergistically increased monocyte and T-cell chemoattractants, expression of adhesion molecules on the endothelial cell surface, and decreased endothelial barrier integrity in vitro, therefore increasing permeability. Our data provide strong evidence of synergism between IFN-γ and TNF- α in inflammatory atherogenesis and provide rationale for dual cytokine antagonism in future studies.
format	article
author	Nehal N. Mehta Heather L. Teague William R. Swindell Yvonne Baumer Nicole L. Ward Xianying Xing Brooke Baugous Andrew Johnston Aditya A. Joshi Joanna Silverman Drew H. Barnes Liza Wolterink Rajan P. Nair Philip E. Stuart Martin Playford John J. Voorhees Mrinal K. Sarkar James T. Elder Katherine Gallagher Santhi K. Ganesh Johann E. Gudjonsson
author_facet	Nehal N. Mehta Heather L. Teague William R. Swindell Yvonne Baumer Nicole L. Ward Xianying Xing Brooke Baugous Andrew Johnston Aditya A. Joshi Joanna Silverman Drew H. Barnes Liza Wolterink Rajan P. Nair Philip E. Stuart Martin Playford John J. Voorhees Mrinal K. Sarkar James T. Elder Katherine Gallagher Santhi K. Ganesh Johann E. Gudjonsson
author_sort	Nehal N. Mehta
title	IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis
title_short	IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis
title_full	IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis
title_fullStr	IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis
title_full_unstemmed	IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis
title_sort	ifn-γ and tnf-α synergism may provide a link between psoriasis and inflammatory atherogenesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2fc891577ed8496cab73a2b9d95b1c7b
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IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis

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