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IL-35 Pretreatment Alleviates Lipopolysaccharide-Induced Acute Kidney Injury in Mice by Inhibiting NF-κB Activation

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Abstract

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-α, IL-6, and IL-1β), 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-κB 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-κB activation and reducing pro-inflammatory cytokine production, and it might represent a novel therapeutic strategy against septic AKI and other inflammatory renal diseases.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 81500572, 81472401), the Science and Technology Key Project on Clinical Medicine of Jiangsu Province (BL2013013), and the Medicine and Hygiene Program of Zhejiang Province (2014KYB231).

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  1. Linkun Hu, Cheng Chen and Jun Zhang have equal contribution.

Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Soochow University, 188 Shizi Rd, Suzhou, 215006, People’s Republic of China

    Linkun Hu, Cheng Chen, Jun Zhang, Xuefeng Zhang & Jianquan Hou

  2. Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore, 117456, Singapore

    Haiyan Liu

  3. Center of Uro-nephrological Disease, Ningbo First Hospital, NO. 59 Liuting Avenue, Haishu District, Ningbo, 315000, People’s Republic of China

    Kerong Wu

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  1. Linkun Hu
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Hu, L., Chen, C., Zhang, J. et al. IL-35 Pretreatment Alleviates Lipopolysaccharide-Induced Acute Kidney Injury in Mice by Inhibiting NF-κB Activation. Inflammation 40, 1393–1400 (2017). https://doi.org/10.1007/s10753-017-0582-9

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