HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Inoue, K.-I. Articles by Yoshikawa, T. Search for Related Content PubMed PubMed Citation Articles by Inoue, K.-I. Articles by Yoshikawa, T.

---

ORIGINAL RESEARCH ARTICLE

Protective Role of Urinary Trypsin Inhibitor in Acute Lung Injury Induced by Lipopolysaccharide

Ken-Ichiro Inoue^*,, Hirohisa Takano^*,,1, Rie Yanagisawa^*, Miho Sakurai^*, Akinori Shimada, Shin Yoshino, Hiroyuki Sato^|| and Toshikazu Yoshikawa

^* Inhalation Toxicology and Pathophysiology Research Team, National Institute for Environmental Studies, Tsukuba, Japan; Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Veterinary Pathology, Faculty of Agriculture, Tottori University, Tottori, Japan; Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Japan; and ^|| Research Center, Mochida Pharmaceutical Company, Ltd., Mochida, Japan

To whom requests for reprints should be addressed at ¹ Inhalation Toxicology and Pathophysiology Research Team, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, 305-0053, Japan. E-mail: htakano{at}nies.go.jp

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 µg/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-1ß, macrophage inflammatory protein-1, 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.

Key Words: urinary trypsin inhibitor • lipopolysaccharide • acute lung injury • cytokines • chemokines • intercellular adhesion molecule

This article has been cited by other articles:

				K.-i. Inoue, H. Takano, T. Yoshikawa, and J.H.J. Vernooy Protease-Antiprotease Imbalance in Inflammatory Diseases in the Lung Chest, August 1, 2005; 128(2): 1069 - 1069. [Full Text] [PDF]