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

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. GaneshJohann E. Gudjonsson

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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.

Original languageEnglish (US)
Article number13831
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis'. Together they form a unique fingerprint.

Cite this