Functional characterization of human IL-8 in vascular stenosis using a novel humanized transgenic mouse model.

Autor: Zhang W; Lemole Center for Integrated Lymphatic and Vascular Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA. Electronic address: wei.zhang0008@temple.edu., Pan L; Lemole Center for Integrated Lymphatic and Vascular Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA; Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, China., Wu X; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA., Slivano OJ; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA., Dong K; Immunology Center of Georgia, Medical College of Georgia at Augusta University, Augusta, GA, USA., Long X; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA.
Jazyk: angličtina
Zdroj: Vascular pharmacology [Vascul Pharmacol] 2024 Oct 30; Vol. 157, pp. 107438. Date of Electronic Publication: 2024 Oct 30.
DOI: 10.1016/j.vph.2024.107438
Abstrakt: IL-8 (aka interleukin 8, CXCL8) is a prototypic cytokine that is highly expressed in the diseased vessel wall and its plasma concentration is strongly associated with cardiovascular events. However, whether IL-8 plays a causative role in cardiovascular diseases remains largely unknown. In this study we used a human IL-8 transgenic (Tg) mouse strain with a bacterial artificial chromosome (BAC) integrated into its genome. This BAC encompasses 166 kb of sequence encompassing the human IL-8 gene locus as well as upstream and downstream DNA sequences containing regulatory elements. This BAC ensured a pathophysiologically regulated, rather than forced constitutive, expression of human IL-8 in the mouse. Tg mice were subjected to complete carotid ligation injury. IL-8 was highly expressed in the ligation-injured carotid artery from 3 days until 2 weeks after injury. As a result, exacerbated neointimal hyperplasia and increased Mac2 and PCNA positive cells were observed in Tg mice. To further confirm its role in promoting neointimal formation, IL-8 was neutralized by anti-IL8 treatment at the ligation site. Consequently, the size of neointima was significantly reduced. Our results provided new insights into the regulation and function of IL-8 in response to vascular insult and during neointima formation.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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