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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doaj-2fc891577ed8496cab73a2b9d95b1c7b2020-12-08T02:30:46ZengNature Publishing GroupScientific Reports2045-23222017-10-017111110.1038/s41598-017-14365-1IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesisNehal N. Mehta0Heather L. Teague1William R. Swindell2Yvonne Baumer3Nicole L. Ward4Xianying Xing5Brooke Baugous6Andrew Johnston7Aditya A. Joshi8Joanna Silverman9Drew H. Barnes10Liza Wolterink11Rajan P. Nair12Philip E. Stuart13Martin Playford14John J. Voorhees15Mrinal K. Sarkar16James T. Elder17Katherine Gallagher18Santhi K. Ganesh19Johann E. Gudjonsson20National Heart Lung and Blood Institute, National Institutes of HealthNational Heart Lung and Blood Institute, National Institutes of HealthDepartment of Dermatology, Univ. of MichiganNational Heart Lung and Blood Institute, National Institutes of HealthDepartment of Dermatology, Case Western Reserve UniversityDepartment of Dermatology, Univ. of MichiganDepartment of Dermatology, Univ. of MichiganDepartment of Dermatology, Univ. of MichiganNational Heart Lung and Blood Institute, National Institutes of HealthNational Heart Lung and Blood Institute, National Institutes of HealthDepartment of Dermatology, Univ. of MichiganDepartment of Dermatology, Univ. of MichiganDepartment of Dermatology, Univ. of MichiganDepartment of Dermatology, Univ. of MichiganNational Heart Lung and Blood Institute, National Institutes of HealthDepartment of Dermatology, Univ. of MichiganDepartment of Dermatology, Univ. of MichiganDepartment of Dermatology, Univ. of MichiganDepartment of Surgery, Division of Vascular Surgery, Univ. of MichiganDepartment of Internal Medicine, Division of Cardiovascular Medicine, and Department of Human Genetics, Univ. of MichiganDepartment of Dermatology, Univ. of MichiganAbstract 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.https://doi.org/10.1038/s41598-017-14365-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-10-01 |
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. |
url |
https://doi.org/10.1038/s41598-017-14365-1 |
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