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

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.