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Ulinastatin Attenuates LPS-Induced Inflammation and Inhibits Endoplasmic Reticulum Stress–Induced Apoptosis in Renal Tubular Epithelial Cells via Regulation of the TLR4/NF-κB and Nrf2/HO-1 Pathways

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Abstract—

Acute kidney injury (AKI) is one of the most common diseases in patients treated in intensive care units. This study was intended to explore the underlying mechanism by which ulinastatin (UTI) influenced the inflammation and apoptosis of renal tubular epithelial cells, HK-2.

The effects of UTI on the cell viability of HK-2 cells were first measured by MTT and lactate dehydrogenase (LDH) detection kit. The apoptosis and inflammation of HK-2 cells were then determined by TUNEL, western blot, ELISA, and RT-qPCR. Then, the proteins in the Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) and nuclear factor erythroid 2–related factor 2 (Nrf2)/Heme oxygenase 1 (HO-1) signaling pathways were measured by western blot for confirming the relationship between UTI and these pathways. Finally, Nrf-2 inhibitor ML385 and TLR4 activator CCL-34 were respectively used on LPS-induced HK-2 cells exposed to UTI for the conduction of gain-of-function and loss-of-function assays.

UTI treatment boosted the cell viability of HK-2 cells damaged by LPS. Furthermore, UTI exposure cut down the apoptosis rate and inhibited the expression inflammatory factors of HK-2 cells induced by LPS. UTI treatment decreased the expression of proteins in the TLR4/NF-κB pathway, increased the HO-1 expression, and prompted the translocation of Nrf2 from the cytoplasm to the nucleus. The alleviated effects of UTI on inflammation and apoptosis LPS-induced HK-2 cells were abolished by ML385 and TLR4, respectively.

UTI attenuates LPS-induced inflammation and inhibits endoplasmic reticulum stress–induced apoptosis in renal tubular epithelial cells by regulating TLR4/NF-κB and Nrf2/HO-1 pathways.

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Author notes

  1. Feixiang Chen and Jiadong Zhu contributed equally.

Authors and Affiliations

  1. ICU, 903RD Hospital of PLA, Hangzhou, 310,013, Zhejiang, China

    Feixiang Chen & Jiadong Zhu

  2. Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, 26400, Shandong, China

    Wei Wang

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  1. Feixiang Chen
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Contributions

Feixiang Chen: project development, data analysis and collection, manuscript writing.

Jiadong Zhu: project development, data analysis and collection, manuscript writing.

Wei Wang: project development, manuscript editing.

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Correspondence to Wei Wang.

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Chen, F., Zhu, J. & Wang, W. Ulinastatin Attenuates LPS-Induced Inflammation and Inhibits Endoplasmic Reticulum Stress–Induced Apoptosis in Renal Tubular Epithelial Cells via Regulation of the TLR4/NF-κB and Nrf2/HO-1 Pathways. Inflammation 44, 2323–2332 (2021). https://doi.org/10.1007/s10753-021-01505-z

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