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. 2017 Oct 23;7:13831. doi: 10.1038/s41598-017-14365-1

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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IFN-γ and TNF-α have synergistic activity on human atherosclerotic tissue ex vivo. (a) CXCL9 and CXCL10 mRNA expression in lesional (PP), non-lesional (PN) and healthy skin (NN), atherosclerotic (athero), healthy vascular tissue (coronary) obtained through RNA-sequencing and shown as FPKM values. (b,c) Atherosclerotic arterial tissue obtained post-amputation was dissected into 3 mm slices and stimulated with a high or low dose of IFN-γ or TNF-α or a combination of both for 6 hours for (b) mRNA expression or 72 hours for (c) protein secretion⁶. Dose-dependent increases in the mRNA expression and protein secretion of CXCL9 and CXCL10 were observed with IFN-γ (0.5, 5 and 50 ng/ml), whereas minimal change in expression was seen with TNF-α stimulation (1 ng/ml or and 10 ng/ml). In contrast, a striking synergistic effect was seen with IFN-γ and TNF-α stimulation (IFN-γ 50 ng/ml, TNF-α at 10 ng/ml). Data are shown as mean ± SEM with 95% CI.