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Kidney Week

Abstract: PO0154

Toll-Like Receptor 4 Blockade Ameliorates Kidney Ischemia-Reperfusion Injury

Session Information

  • AKI Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Jung, Su Woong, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
  • Jung-Woo, Seo, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
  • Kim, Yang gyun, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
  • Moon, Ju young, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
  • Lee, Sangho, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
Background

Renal ischemia-reperfusion injury (IRI) is a key mechanism in various clinical conditions including sepsis and transplantation, and animal studies have demonstrated that toll-like receptor 4 (TLR4) is a key mediator of IRI. Since few study have tried the pharmacolgic inhibition of TLR4 in renal IRI, we investigated the effect of TLR4 blockade on this condition with the goal of persuing better therapeutic options.

Methods

We subjected C57BL/6 mice to 23 minutes of renal pedicle clamping following an intraperitoneal injection of TLR inhibitory peptide (TIP1), a TLR4 inhibitor, or vehicle. Sham mice underwent only a flank incision. Then, the kidneys were harvested after 24 hours of reperfusion for histology, western blot, RT-PCR, and flow cytometry. We also performed primary mouse renal tubular cell culture to assess the effects of TLR4 inhibition on tubular epithelial cells under hypoxia and subsequent reoxygenation.

Results

TIP1 pretreatment lowered the magnitude of an increase in serum creatinine levels and attenuated tubular injury. In addition, TIP1 administration decreased mRNA expressions of inflammatory cytokines, and apoptotic cells, and lowered oxidative stress in postischemic kidneys. The kidneys pretreated with TIP1 also showed less infiltration of macrophages and T helper 17 cells. In primary mouse tubular cells subjected to hypoxia and reoxygenation, the addition of TIP1 into culture media ameliorated the magnitude of an increase in mRNA levels of KIM1 and inflammatory cytokines.

Conclusion

Our data demonstrated that inhibition of TLR4 with TIP1 reduced tubular injury and an inflammatory and immune response in a mouse model of IRI.

Funding

  • Government Support - Non-U.S.