Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells

Abstract Macrophage migration inhibitory factor (MIF) is a non-canonical cytokine that is involved in multiple inflammatory diseases, including atherosclerosis. High MIF expression found in leukocytes which facilitates the initiation and progression of atherosclerosis. However, little is known about...

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Autores principales:	Congzhen Qiao, Shengdi Li, Haocheng Lu, Fan Meng, Yanbo Fan, Yanhong Guo, Y. Eugene Chen, Jifeng Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b4808f9e8b04967be4c1f6c534fb72e
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spelling	oai:doaj.org-article:5b4808f9e8b04967be4c1f6c534fb72e2021-12-02T15:08:43ZLaminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells10.1038/s41598-018-20885-12045-2322https://doaj.org/article/5b4808f9e8b04967be4c1f6c534fb72e2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20885-1https://doaj.org/toc/2045-2322Abstract Macrophage migration inhibitory factor (MIF) is a non-canonical cytokine that is involved in multiple inflammatory diseases, including atherosclerosis. High MIF expression found in leukocytes which facilitates the initiation and progression of atherosclerosis. However, little is known about biomechanical forces in the induction of MIF in endothelial cells (ECs). Here, we show that laminar shear stress (LS) inhibits the expression of MIF in ECs. By profiling the whole transcriptome of human coronary artery ECs under different shear stress, we found that athero-protective LS attenuates the expression of MIF whereas pro-atherosclerotic oscillatory shear stress (OS) significantly increased the expression of MIF. En face staining of rabbit aorta revealed high MIF immunoreactivity in lesser curvature as well as arterial bifurcation areas where OS is predominant. Mechanistically, we found that Krüpple like factor 2 (KLF2) is required for inhibition of MIF expression in ECs in the context of shear stress. Knockdown of KLF2 abolishes LS-dependent MIF inhibition while overexpression of KLF2 significantly attenuated MIF expression. Overall, the present work showed that MIF is a shear stress-sensitive cytokine and is transcriptionally regulated by KLF2, suggesting that LS exerts its athero-protective effect in part by directly inhibiting pro-inflammatory MIF expression.Congzhen QiaoShengdi LiHaocheng LuFan MengYanbo FanYanhong GuoY. Eugene ChenJifeng ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Congzhen Qiao Shengdi Li Haocheng Lu Fan Meng Yanbo Fan Yanhong Guo Y. Eugene Chen Jifeng Zhang Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells
description	Abstract Macrophage migration inhibitory factor (MIF) is a non-canonical cytokine that is involved in multiple inflammatory diseases, including atherosclerosis. High MIF expression found in leukocytes which facilitates the initiation and progression of atherosclerosis. However, little is known about biomechanical forces in the induction of MIF in endothelial cells (ECs). Here, we show that laminar shear stress (LS) inhibits the expression of MIF in ECs. By profiling the whole transcriptome of human coronary artery ECs under different shear stress, we found that athero-protective LS attenuates the expression of MIF whereas pro-atherosclerotic oscillatory shear stress (OS) significantly increased the expression of MIF. En face staining of rabbit aorta revealed high MIF immunoreactivity in lesser curvature as well as arterial bifurcation areas where OS is predominant. Mechanistically, we found that Krüpple like factor 2 (KLF2) is required for inhibition of MIF expression in ECs in the context of shear stress. Knockdown of KLF2 abolishes LS-dependent MIF inhibition while overexpression of KLF2 significantly attenuated MIF expression. Overall, the present work showed that MIF is a shear stress-sensitive cytokine and is transcriptionally regulated by KLF2, suggesting that LS exerts its athero-protective effect in part by directly inhibiting pro-inflammatory MIF expression.
format	article
author	Congzhen Qiao Shengdi Li Haocheng Lu Fan Meng Yanbo Fan Yanhong Guo Y. Eugene Chen Jifeng Zhang
author_facet	Congzhen Qiao Shengdi Li Haocheng Lu Fan Meng Yanbo Fan Yanhong Guo Y. Eugene Chen Jifeng Zhang
author_sort	Congzhen Qiao
title	Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells
title_short	Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells
title_full	Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells
title_fullStr	Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells
title_full_unstemmed	Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells
title_sort	laminar flow attenuates macrophage migration inhibitory factor expression in endothelial cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/5b4808f9e8b04967be4c1f6c534fb72e
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Laminar Flow Attenuates Macrophage Migration Inhibitory Factor Expression in Endothelial Cells

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