Activated protein C inhibits lung injury induced by LPS via downregulating MAPK signaling

Zhou,Jianming; Hu,Ruoyu; Jing,Shengjie; Xue,Xin; Tang,Wenhao

doi:10.3892/etm.2018.6228

Activated protein C inhibits lung injury induced by LPS via downregulating MAPK signaling

Authors:
- Jianming Zhou
- Ruoyu Hu
- Shengjie Jing
- Xin Xue
- Wenhao Tang
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Affiliations: Department of Thoracic Surgery, Southeast University Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China
Published online on: May 29, 2018 https://doi.org/10.3892/etm.2018.6228
Pages: 931-936

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Abstract

The aim of the present study was to investigate the effect and the underlying mechanism of activated protein C (APC) in lipopolysaccharide (LPS) induced lung injury, as well as the potential mechanism. According to the treatment, 50 rats were randomly divided into 5 groups: Control, model (LPS), low‑dose group [LPS + 0.1 mg/kg recombined human activated protein C (rhAPC)], median‑dose group (LPS + 0.3 mg/kg rhAPC) and high‑dose group (LPS + 0.5 mg/kg rhAPC). Then, inflammation in the lung was assessed using hematoxylin and eosin (H&E) staining. Following the collection of bronchoalveolar lavage fluid (BALF), the number of leukocytes and neutrophils in BALF was counted, and superoxide dismutase (SOD) activity was assessed, as well as the expression levels of interleukin (IL)‑1β, IL‑6 and tumor necrosis factor (TNF)‑α using ELISA. Subsequently, the expression and phosphorylation of P‑38, extracellular signal‑regulated kinase (Erk)‑1/2, and c‑Jun N‑terminal kinase (JNK) were estimated using western blotting. Based on H&E staining, rhAPC markedly suppressed inflammatory infiltration in the lung induced by LPS in a dose‑dependent manner. In addition, rhAPC also significantly attenuated the accumulation of leptocytes and neutrophils, and the reduction of SOD in BALF induced by LPS in a dose‑dependent manner. rhAPC also significantly attenuated the elevation of IL‑1β, IL‑6 and TNF‑α in BALF induced by LPS in a dose‑dependent manner. Further mechanistic analysis revealed that rhAPC treatment could evidently attenuate the phosphorylation levels of P‑38, Erk1/2 and JNK in the lung induced by LPS in a dose‑dependent manner. In conclusion, APC significantly alleviated the lung inflammation induced by LPS by downregulating the phosphorylation of P‑38, ERK1/2 and JNK.

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