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Inflammation

Inflammation

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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

Published:1 December 2021 DOI: 10.1007/s10753-021-01505-z PMID: 34585338
Feixiang Chen, Jiadong Zhu, Wei Wang

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.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
ML385 846557-71-9 C29H25N3O4S 154 suppliers $18.00-$2646.00
ML385 846557-71-9 C29H25N3O4S 154 suppliers $18.00-$2646.00
ML385 846557-71-9 C29H25N3O4S 154 suppliers $18.00-$2646.00
ML385 846557-71-9 C29H25N3O4S 154 suppliers $18.00-$2646.00

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