IL-35 Pretreatment Alleviates Lipopolysaccharide-Induced Acute Kidney Injury in Mice by Inhibiting NF-κB Activation
IL-35 Pretreatment Alleviates Lipopolysaccharide-Induced Acute Kidney Injury in Mice by Inhibiting NF-κB Activation
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IL-35 预处理通过抑制 NF-κ B 激活减轻脂多糖诱导的小鼠急性肾损伤
DOI：
10.1007/s10753-017-0582-9
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发表时间：
2017-08-01
期刊：
影响因子：
5.1
通讯作者：
Hou, Jianquan
中科院分区：
文献类型：
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作者：
Hu, Linkun;Chen, Cheng;Hou, Jianquan
脓毒性急性肾损伤（AKI）是一个高死亡率的公共卫生问题。抑制过度活跃的炎症被认为是治疗脓毒性AKI的一种有希望的策略。本研究评估了IL-12细胞因子家族中独特的免疫抑制成员白细胞介素(IL -35) -35对脂多糖（LPS）诱导小鼠AKI的预防作用，发现与空白载体对照小鼠相比，编码IL-35的质粒（pIL-35）预处理小鼠的肾功能明显改善，血尿素氮（BUN）和血清肌酐（SCr）降低，肾脏病理改变明显减轻。为了探索其潜在的保护机制，我们发现pIL-35治疗可以显著减少肾促炎细胞因子（tnf - α、IL-6和IL-1 β）的产生，而对IL-10（一种抗炎细胞因子）没有显著影响。此外，我们的研究结果显示，IL-35预处理可能潜在地抑制lps诱导的AKI小鼠肾nf - κ B信号通路的激活。综上所述，我们的研究表明，IL-35预处理可以通过抑制NF-kappa B的激活和减少促炎细胞因子的产生，有效预防lps诱导的AKI，可能是一种治疗脓毒性AKI和其他炎症性肾脏疾病的新策略。
Septic acute kidney injury (AKI) is a public health problem with high mortality. Suppression of over-active inflammation is considered as a promising strategy for septic AKI. In this study, we evaluated the prophylactic effect of interleukin (IL)-35, the unique immune-suppressive member of IL-12 cytokine family, on lipopolysaccharide (LPS)-induced AKI in mice, and found that compared with control mice given empty vector, mice pretreated with plasmid encoding IL-35 (pIL-35) significantly improved renal function indicated by reduced blood urea nitrogen (BUN) and serum creatinine (SCr), and obviously alleviated renal pathological changes. To explore the underlying protective mechanisms, we found that pIL-35 treatment could robustly reduce the production of renal pro-inflammatory cytokines (TNF-alpha, IL-6, and IL-1 beta), with no significant impact on IL-10, an anti-inflammatory cytokine. Furthermore, our results revealed that IL-35 pretreatment could potentially inhibit the activation of renal NF-kappa B signaling pathway in LPS-induced AKI mice. Taken together, our study indicated that IL-35 pretreatment could efficiently prevent LPS-induced AKI via inhibiting NF-kappa B activation and reducing pro-inflammatory cytokine production, and it might represent a novel therapeutic strategy against septic AKI and other inflammatory renal diseases.