Inhibition of HtrA2 alleviates inflammatory response and cell apoptosis in lipopolysaccharide‑induced acute pneumonia in rats

Wang,Xin

doi:10.3892/mmr.2020.11410

Inhibition of HtrA2 alleviates inflammatory response and cell apoptosis in lipopolysaccharide‑induced acute pneumonia in rats

Authors:
- Xin Wang
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Affiliations: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China
Published online on: August 4, 2020 https://doi.org/10.3892/mmr.2020.11410
Pages: 3127-3134
Copyright: © Wang . This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pneumonia is one of the commonest causes of death worldwide. High‑temperature requirement A2 (HtrA2) is a proapoptotic mitochondrial serine protease involved in caspase‑dependent or caspase‑independent cell apoptosis. UCF‑101 (5‑[5‑(2‑nitrophenyl) furfuryl iodine]‑1,3‑diphenyl‑2‑thiobarbituric acid), an inhibitor of HtrA2, has a protective effect on organs in various diseases by inhibiting cell apoptosis. The aim of the present study was to explore whether UCF‑101 has a protective effect on lungs in pneumonia. A lipopolysaccharide (LPS)‑induced pneumonia model was established in rats. UCF‑101 (2 µmol/kg) was used for treatment. Lung injury was detected by hematoxylin and eosin staining. Pro‑inflammatory cytokines and oxidative stress‑related factors were detected using corresponding test kits. TUNEL staining was used to measure the amount of cell apoptosis. Apoptosis‑associated proteins were detected by western blot assay. The present study indicated pulmonary injury induced by LPS. Treatment with UCF‑101 clearly alleviated this pulmonary damage and restored the levels of pro‑inflammatory cytokines and oxidative stress‑related factors. In addition, UCF‑101 significantly reduced LPS‑induced cell apoptosis, the release of HtrA2 and cytochrome from mitochondria to the cytoplasm and inhibited the expression of pro‑apoptotic proteins. UCF‑101 also restored the ATP level. The present results demonstrated that UCF‑101 acts as a positive regulator of acute pneumonia by inhibiting inflammatory response, oxidative stress and mitochondrial apoptosis. The present study suggests UCF‑101 as a potential candidate for pneumonia therapy.

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