Urinary trypsin inhibitor attenuates lipopolysaccharide-induced acute lung injury by blocking the activation of p38 mitogen-activated protein kinase.
OBJECTIVE
To investigate the protective effect of urinary trypsin inhibitor (UTI) in a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the underlying molecular mechanism.


METHODS
Rats were randomly assigned into three groups: control group, LPS treatment group and LPS/UTI treatment group. The serum concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-10 were measured by ELISA. The expression of p38 mitogen-activated protein kinase (MAPK) in lung tissues was determined by Western blot analysis.


RESULTS
Administration of UTI reduced the lung wet/dry weight ratio and ameliorated the tissue damage. In the LPS/UTI treatment group, levels of TNF-α were significantly lower than those in the LPS treatment group, while the levels of IL-10 were significantly higher than those in the LPS treatment group. Western blot analysis revealed that UTI inhibited the phosphorylation of p38 MAPK in lung tissues.


CONCLUSIONS
UTI attenuates LPS-induced ALI, probably by adjusting the balance between proinflammatory and anti-inflammatory cytokines. The mechanism responsible for the decreased TNF-α expression may be related to the inhibitory effect of UTI on p38 MAPK activation.
Department of Pediatrics, Provincial Hospital Affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan, 250021, China. zhangxy912@126.com
Xinying
X
Zhang
Fengqin
F
Liu
Haiyan
H
Liu
Hongxia
H
Cheng
Wei
W
Wang
Qiang
Q
Wen
Yulin
Y
Wang
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D006023:Glycoproteins / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014361:Trypsin Inhibitors / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D006023:Glycoproteins; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases; C028665:urinastatin
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