Background

CKD is a major cause of morbidity and mortality worldwide. Considerable evidence now indicates that renal inflammation plays a central role in the initiation and progression of CKD. Recent investigations have demonstrated that IFNλ plays an important role in the pathogenesis of autoimmune and inflammatory diseases. However, the association of IFNλ with CKD is still poorly understood.

Objective

To analyze the correlation between IFNλ levels and pro-inflammatory cytokines, and to investigate the effect of IFNλ on PBMCs in patients with CKD.

Methods

PBMCs were harvested from patients with CKD and healthy controls for measuring the expression level of inflammatory cytokines by RT-qPCR. Spearman correlation test was used to analyze correlation between IFNλ and cytokines as well as eGFR. PBMCs from healthy individuals and CKD patients were subjected to IFNλ protein stimulation. IL6, TNFα, IL10, ISG15 and MX1 mRNA level were measured by RT-PCR, STAT1 and phosphorylated STAT1 protein level were measured by Western blot.

Results

Patients with CKD showed higher levels of IFNλ in PBMCs compared to healthy controls. IFNλ mRNA levels were associated with cytokines and eGFR. The transcription of IL6, TNFα, and IL10 was significantly increased in healthy human PBMCs after IFNλ stimulation. In addition, IFNλ acts on PBMCs by p-STAT1 and ISG15 as well as MX1.

Conclusion

High expression of IFNλ was found in CKD patients and was associated with eGFR and disease-related cytokines. More importantly, IFNλ promoted the expression of pro-inflammatory cytokines in PBMCs, suggesting a potential pro-inflammatory role of IFNλ in CKD.

中文翻译：

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干扰素 lambda 调节慢性肾病患者 PBMC 中促炎细胞因子的产生

背景

CKD 是全世界发病和死亡的主要原因。现在大量证据表明肾脏炎症在 CKD 的发生和进展中发挥着核心作用。最近的研究表明，IFNλ在自身免疫性疾病和炎症性疾病的发病机制中发挥着重要作用。然而，人们对 IFNλ 与 CKD 的关系仍知之甚少。

客观的

分析IFNλ水平与促炎细胞因子的相关性，探讨IFNλ对CKD患者PBMC的影响。

方法

从 CKD 患者和健康对照中采集 PBMC，通过 RT-qPCR 测量炎症细胞因子的表达水平。采用Spearman相关性检验分析IFNλ与细胞因子以及eGFR之间的相关性。来自健康个体和 CKD 患者的 PBMC 接受 IFNλ 蛋白刺激。RT-PCR测定IL6、TNFα、IL10、ISG15和MX1 mRNA水平，Western blot测定STAT1和磷酸化STAT1蛋白水平。

结果

与健康对照相比，CKD 患者的 PBMC 中 IFNλ 水平较高。IFNλ mRNA 水平与细胞因子和 eGFR 相关。IFNλ 刺激后，健康人 PBMC 中 IL6、TNFα 和 IL10 的转录显着增加。此外，IFNλ通过p-STAT1和ISG15以及MX1作用于PBMC。

结论

在 CKD 患者中发现 IFNλ 高表达，并且与 eGFR 和疾病相关细胞因子相关。更重要的是，IFNλ促进PBMC中促炎细胞因子的表达，表明IFNλ在CKD中具有潜在的促炎作用。