Esfahani Maryam, Saidijam Masoud, Najafi Rezvan, Goodarzi Mohammad Taghi, Movahedian Ahmad
Isfahan Pharmaceutical Sciences Research Center AND Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Professor, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
ARYA Atheroscler. 2018 Jan;14(1):1-10. doi: 10.22122/arya.v14i1.1602.
Atherosclerosis is one of the predominant causes of cardiovascular disease (CVD). Several studies indicated the significant pathophysiological role of salusin-β in atherosclerosis. Cytokines are involved in all stages of atherosclerosis. Therefore, we aimed to assess the effect of salusin-β on interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18) (as inflammatory cytokines) and interleukin 1Ra (IL-1Ra) (as anti-inflammatory cytokines) levels in human umbilical vein endothelial cells (HUVECs).
The HUVECs were cultured in HUVEC completed medium and treated with different doses of salusin-β for 6 and 12 hours. For the investigation of nuclear factor ƙβ (NF-ƙβ) signaling pathway involvement, cells were treated in the presence or absence of Bay 11-7082 (as NF-ƙβ inhibitor). The mRNA expression and protein level of cytokines were measured by a real-time polymerase chain reaction (PCR) system and enzyme-linked immunosorbent assay (ELISA) method, respectively.
Salusin-β increased mRNA expression and protein level of IL-6, IL-8 and IL-18. This protein decreased mRNA and protein level of IL-1Ra in HUVECs. NF-ƙβ signaling pathway was involved in the up-regulatory effect of salusin-β on mRNA expression of pro-inflammatory cytokines. The down-regulatory effect of salusin-β on IL-1Ra expression could not be influenced by Bay 11-7082 pre-treatment.
It seems that salusin-β may participate in a cascade pathway in vascular inflammation. Our findings suggested that salusin-β has potential use as a therapeutic target for atherosclerosis.
动脉粥样硬化是心血管疾病(CVD)的主要病因之一。多项研究表明,salusin-β在动脉粥样硬化中具有重要的病理生理作用。细胞因子参与动脉粥样硬化的各个阶段。因此,我们旨在评估salusin-β对人脐静脉内皮细胞(HUVECs)中白细胞介素6(IL-6)、白细胞介素8(IL-8)、白细胞介素18(IL-18)(作为炎性细胞因子)和白细胞介素1受体拮抗剂(IL-1Ra)(作为抗炎细胞因子)水平的影响。
将HUVECs培养于HUVEC完全培养基中,并用不同剂量的salusin-β处理6小时和12小时。为研究核因子κβ(NF-κβ)信号通路的参与情况,细胞在有或无Bay 11-7082(作为NF-κβ抑制剂)的情况下进行处理。分别通过实时聚合酶链反应(PCR)系统和酶联免疫吸附测定(ELISA)法检测细胞因子的mRNA表达和蛋白水平。
Salusin-β增加了IL-6、IL-8和IL-18的mRNA表达和蛋白水平。该蛋白降低了HUVECs中IL-1Ra的mRNA和蛋白水平。NF-κβ信号通路参与了salusin-β对促炎细胞因子mRNA表达的上调作用。Bay 11-7082预处理不影响salusin-β对IL-1Ra表达的下调作用。
似乎salusin-β可能参与血管炎症的级联途径。我们的研究结果表明,salusin-β有潜力作为动脉粥样硬化的治疗靶点。