Protective role of urinary trypsin inhibitor in acute lung injury induced by lipopolysaccharide.
Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used as a drug for patients with acute inflammatory disorders such as disseminated intravascular coagulation, shock, and pancreatitis. However, direct contribution of UTI to inflammatory diseases has not been established. The present study analyzed acute inflammatory lung injury induced by lipopolysaccharide (LPS) in UTI-deficient (-/-) mice and corresponding wild-type (WT) mice. UTI (-/-) and WT mice were treated intratracheally with vehicle or LPS (125 mug/kg). The cellular profile of bronchoalveolar lavage fluid, lung water content, histology, and expression of proinflammatory molecules in the lung were evaluated. After LPS challenge, both genotypes of mice revealed neutrophilic lung inflammation and pulmonary edema. UTI (-/-) mice, however, showed more prominent infiltration of inflammatory cells and edema than WT mice. After LPS challenge in both genotypes of mice, the lung levels of mRNA and/or protein expression of interleukin-1beta, macrophage inflammatory protein-1alpha, macrophage chemoattractant protein-1, keratinocyte chemoattractant, and intercellular adhesion molecule-1 (ICAM-1) were elevated in both groups, but to a greater extent in UTI (-/-) mice than in WT mice. These results suggest that UTI protects against acute lung injury induced by bacterial endotoxin, at least partly, through the inhibition of the enhanced local expression of proinflammatory cytokines, chemokines, and ICAM-1.
Inoue
Ken-Ichiro
K
Inhalation Toxicology and Pathophysiology Research Team, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, 305-0053, Japan.
Takano
Hirohisa
H
Yanagisawa
Rie
R
Sakurai
Miho
M
Shimada
Akinori
A
Yoshino
Shin
S
Sato
Hiroyuki
H
Yoshikawa
Toshikazu
T
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000032:analysis / Q000037:antagonists & inhibitors; D002630:Chemotactic Factors / Q000032:analysis; D016207:Cytokines / Q000032:analysis / Q000037:antagonists & inhibitors; D006023:Glycoproteins / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages; D051379:Mice; D018345:Mice, Knockout; D020011:Protective Agents / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000209:etiology; D012333:RNA, Messenger / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014361:Trypsin Inhibitors / Q000627:therapeutic use*
D018925:Chemokines; D002630:Chemotactic Factors; D016207:Cytokines; D006023:Glycoproteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D020011:Protective Agents; D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D018799:Intercellular Adhesion Molecule-1; C028665:urinastatin