Methylprednisolone alleviates LPS-induced acute lung injury by inhibiting STAT3-ERK1/2 signaling pathway
10.3760/cma.j.issn.1671-0282.2019.10.017
- VernacularTitle: 甲基强的松龙抑制STAT3-ERK1/2通路改善脂多糖诱导急性肺损伤
- Author:
Jia SONG
1
;
Chunxia WANG
;
Xi XIONG
;
Yuqian REN
;
Yucai ZHANG
Author Information
1. Department of Critical Care Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong University, 200062 Shanghai, China
- Publication Type:Journal Article
- Keywords:
Methylprednisolone;
STAT3;
ERK1/2;
Lipopolysaccharide;
Acute lung injury;
Sepsis;
TNF-α
;
IL-6
- From:
Chinese Journal of Emergency Medicine
2019;28(10):1266-1271
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of methylprednisolone on STAT3-ERK1/2 signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI).
Methods:The C57BL/6J male mice (8-week-old) were randomly(random number) divided into 4 groups: control group (control), LPS-induced endotoxemia model (LPS), only methylprednisolone (MP) administration group (MP), and intervention group with 2 mg/kg MP (LPS+MP) (n= 8 per group). The wet/dry (W/D) weight ratio of lung tissue, lung pathology by hematoxylin & eosin (HE) staining, serum and mRNA levels of TNF-α and IL-6 in lungs were determined. The protein levels of p-STAT3 and p-ERK1/2 in lungs were detected by Western blot. Statistical analyses were performed using One-way analysis of variance test to compare among multiple groups.
Results:(1)MP treatment significantly decreased the lung W/D weight ratio compared with the LPS group[(3.01±0.84) vs(3.87±0.17), P = 0.038]; (2) The histopathological lesions of the lung were improved in the LPS+MP group compared with the LPS group accompanied with reduced inflammatory cell infiltration and attenuated the alveolar wall thickening; (3) The serum levels of TNF-α and IL-6 in the LPS+MP group was significantly decreased compared with the LPS group[(3.17±1.64) pg/mL vs (6.61±1.27) pg/mL, P = 0.003; (1.42±0.35) pg/mL vs (3.80±1.35) pg/mL, P = 0.008, respectively], and the mRNA levels of TNF-α and IL-6 in the LPS+MP group were significantly lower than those of the LPS group [(5.10±0.81) vs (12.2±5.05), P = 0.03; (1.62±1.00) vs (11.12±6.56), P=0.026; respectively]; (4) MP therapy significantly inhibited P-STAT3 and P-ERK1/2 protein levels [(0.26±0.05) vs (0.86±0.06), P < 0.001, (0.24±0.02) vs (1.34±0.32), P < 0.001].
Conclusions:Methylprednisolone protects LPS-induced acute lung injury possibly via suppressing STAT3-ERK1/2 signaling pathway and reducing TNF-α and IL-6 expression.
