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

Inflammation. 2017 Aug;40(4):1393-1400. doi: 10.1007/s10753-017-0582-9.

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.

Keywords: IL-35; NF-κB; acute kidney injury; prevention; sepsis.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / pathology
  • Animals
  • Cytokines / drug effects
  • Inflammation
  • Interleukins / therapeutic use*
  • Kidney / drug effects
  • Kidney / physiology
  • Lipopolysaccharides
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism

Substances

  • Cytokines
  • Interleukins
  • Lipopolysaccharides
  • NF-kappa B
  • interleukin-35, mouse