Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Diagnostic Laboratory of Sciences and Technology Research Center, Paramedical School, Shiraz University of Medical Sciences, Shiraz, Iran.
Int Immunopharmacol. 2021 Dec;101(Pt A):108295. doi: 10.1016/j.intimp.2021.108295. Epub 2021 Nov 1.
Toll-like receptors (TLRs) are among the players of inflammation during atherosclerosis. We assessed the effects of Eritoran, a TLR-4 antagonist, on lipopolysaccharide (LPS)-induced cytokines production by Peripheral Blood Mononuclear Cells (PBMCs) of patients with high-stenosis (HS) (n = 6) and healthy controls (HCs) (n = 6) co-cultured with Human Umbilical Vein Endothelial Cells (HUVECs). LPS stimulation significantly increased the levels of IL-6 (P = 0.007 and P = 0.005), TNF-α (P = 0.006 and P = 0.005), IL-2 (P = 0.007 and P = 0.002), IFN-γ (P = 0.006 and P = 0.003), IL-17A (P = 0.004 and P = 0.003), IL-17F (P = 0.005 and P = 0.003), IL-5 (P = 0.007 and P = 0.005), IL-13 (P = 0.006 and P = 0.005), IL-9 (P = 0.005 and P = 0.005) and IL-21 (P = 0.007 and P = 0.005) in HUVECs co-cultured with HC and HS PBMCs as compared with un-stimulated co-culture condition, respectively. Eritoran treatment (50 μg/mL and 100 μg/mL) significantly reduced the levels of LPS-induced IL-6 (P = 0.007 and P = 0.006; P = 0.007 and P = 0.007), TNF-α (P = 0.005 and P = 0.003; P = 0.007 and P = 0.005), IL-2 (P = 0.007 and P = 0.005; P = 0.005 and P = 0.004), IFN-γ (P = 0.007 and P = 0.005; P = 0.005 and P = 0.004), IL-17A (P = 0.005 and P = 0.002; P = 0.005 and P = 0.002), IL-17F (P = 0.006 and P = 0.006; P = 0.005 and P = 0.005), IL-5 (P = 0.007 and P = 0.006; P = 0.007 and P = 0.007), IL-9 (P = 0.005 and P = 0.005; P = 0.005 and P = 0.005) and IL-21 (P = 0.007 and P = 0.007; P = 0.005 and P = 0.005) in stimulated HUVECs co-cultured with HC and HS PBMCs, compared to un-treated condition, respectively. Our results demonstrate that attenuating effect of Eritoran on the inflammatory responses to LPS is higher in PBMCs of patients with high stenosis, suggesting its potential role in ameliorating inflammatory conditions in atherosclerosis.
Toll 样受体 (TLRs) 是动脉粥样硬化炎症反应的参与者之一。我们评估了 TLR-4 拮抗剂 Eritoran 对高狭窄 (HS) 患者 (n = 6) 和健康对照者 (HCs) (n = 6) 的外周血单核细胞 (PBMCs) 与人脐静脉内皮细胞 (HUVECs) 共培养后 LPS 诱导细胞因子产生的影响。LPS 刺激显著增加了 IL-6 (P = 0.007 和 P = 0.005)、TNF-α (P = 0.006 和 P = 0.005)、IL-2 (P = 0.007 和 P = 0.002)、IFN-γ (P = 0.006 和 P = 0.003)、IL-17A (P = 0.004 和 P = 0.003)、IL-17F (P = 0.005 和 P = 0.003)、IL-5 (P = 0.007 和 P = 0.005)、IL-13 (P = 0.006 和 P = 0.005)、IL-9 (P = 0.005 和 P = 0.005) 和 IL-21 (P = 0.007 和 P = 0.005) 在与未刺激共培养条件相比，与 HC 和 HS PBMC 共培养的 HUVECs 中的水平。Eritoran 治疗 (50μg/mL 和 100μg/mL) 显著降低 LPS 诱导的 IL-6 (P = 0.007 和 P = 0.006；P = 0.007 和 P = 0.007)、TNF-α (P = 0.005 和 P = 0.003；P = 0.007 和 P = 0.005)、IL-2 (P = 0.007 和 P = 0.005；P = 0.005 和 P = 0.004)、IFN-γ (P = 0.007 和 P = 0.005；P = 0.005 和 P = 0.004)、IL-17A (P = 0.005 和 P = 0.002；P = 0.005 和 P = 0.002)、IL-17F (P = 0.006 和 P = 0.006；P = 0.005 和 P = 0.005)、IL-5 (P = 0.007 和 P = 0.006；P = 0.007 和 P = 0.007)、IL-9 (P = 0.005 和 P = 0.005；P = 0.005 和 P = 0.005) 和 IL-21 (P = 0.007 和 P = 0.007；P = 0.005 和 P = 0.005) 在与 HC 和 HS PBMC 共培养的刺激 HUVECs 中的水平，与未处理条件相比，分别。我们的结果表明，Eritoran 对 LPS 诱导的炎症反应的抑制作用在高狭窄患者的 PBMC 中更高，这表明其在改善动脉粥样硬化炎症状态中的潜在作用。
