Abstract
The balance between pro- and anti-inflammatory cytokines released by immune and non-immune cells plays a decisive role in the progression of atherosclerosis. Interleukin (IL)-17A has been shown to accelerate atherosclerosis. In this study, we investigated the effect on pro-inflammatory mediators and atherosclerosis development of an Affibody molecule that targets IL17A. Affibody molecule neutralizing IL17A, or sham were administered in vitro to human aortic smooth muscle cells (HAoSMCs) and murine NIH/3T3 fibroblasts and in vivo to atherosclerosis-prone, hyperlipidaemic ApoE−/− mice. Levels of mediators of inflammation and development of atherosclerosis were compared between treatments. Exposure of human smooth muscle cells and murine NIH/3T3 fibroblasts in vitro to αIL-17A Affibody molecule markedly reduced IL6 and CXCL1 release in supernatants compared with sham exposure. Treatment of ApoE−/− mice with αIL-17A Affibody molecule significantly reduced plasma protein levels of CXCL1, CCL2, CCL3, HGF, PDGFB, MAP2K6, QDPR, and splenocyte mRNA levels of Ccxl1, Il6, and Ccl20 compared with sham exposure. There was no significant difference in atherosclerosis burden between the groups. In conclusion, administration of αIL17A Affibody molecule reduced levels of pro-inflammatory mediators and attenuated inflammation in ApoE−/− mice.
Highlights
Interleukin (IL)-17A plays a critical role in the development of various chronic inflammatory diseases including inflammatory bowel disease, rheumatoid arthritis, and experimental autoimmune encephalitis through the actions of CD4+ T helper 17 (Th17) cells [3]
We investigate the effect of αIL17A Affibody molecule and found that αIL17A Affibody molecule reduced IL6 and CXCL1 release by human smooth muscle cells and murine NIH/3T3 fibroblasts
Together with the observations of reduced hepatocyte growth factor (HGF), PDGBF, MAP2K6, and quinonoid dihydropyridine reductase (QDPR), these results suggest that the novel Affibody molecule effectively blocks IL17A and attenuates circulating inflammatory markers and other atherosclerosisassociated proteins
Summary
Innate and adaptive immunity are key in the formation and progression of atherosclerotic lesions and in plaque rupture [1, 2]. Lipid loaded macrophages and T cells accumulate in the vascular wall and promote initiation and progression of atherosclerosis [1]. Interleukin (IL)-17A plays a critical role in the development of various chronic inflammatory diseases including inflammatory bowel disease, rheumatoid arthritis, and experimental autoimmune encephalitis through the actions of CD4+ T helper 17 (Th17) cells [3]. IL17A controls the immune responses against extracellular bacteria and fungi [3]. IL17A is mainly produced by CD4+ Th17 cells. IL17A is produced by other cells including CD8+ T cells, Targeting IL17A Using an Affibody Molecule
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