QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.104.005967v1 67/3/673    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 ARTICLE

Urinary Trypsin Inhibitor Protects against Systemic Inflammation Induced by Lipopolysaccharide

Inhalation Toxicology and Pathophysiology Research Team, National Institute for Environmental Studies, Tsukuba, Japan (K.-I., H.T., R.Y., M.S.); Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan (H.T, T.Y.); Department of Veterinary Pathology, Faculty of Agriculture, Tottori University, Tottori, Japan (A.S.); Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Japan (S.Y.); and Research Center, Mochida Pharmaceutical Company, Ltd., Shizuoka, Japan (H.S.)

Abstract

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 in Japan. Recent studies have demonstrated that serine protease inhibitors may play an anti-inflammatory role beyond merely an inhibitory action on neutrophil elastase at the site of inflammation at least in vitro. To clarify the direct contributions of UTI to inflammatory condition in vivo, we analyzed its roles in experimental systemic inflammatory response induced by intraperitoneal administration of lipopolysaccharide (LPS) using UTI deficient (–/–) mice and corresponding wild-type (WT) mice. After LPS (1 mg/kg) challenge, UTI (–/–) mice revealed a significant elevation of plasma fibrinogen and fibrinogen/fibrin degradation products and a decrease in white blood cell counts compared with WT mice. LPS treatment induced more severe neutrophilic inflammation in the lung and the kidney obtained from UTI (–/–) mice than in those from WT mice, which was confirmed by histological examination. The protein levels of proinflammatory mediators, such as macrophage chemoattractant protein (MCP)-1 in the lungs, MCP-1 and keratinocyte chemoattractant (KC) in the kidneys, and interleukin-1, macrophage inflammatory protein-2, MCP-1, and KC in the liver, were significantly greater in UTI (–/–) mice than in WT mice after LPS challenge. Our results suggest that UTI protects against systemic inflammatory response and subsequent organ injury induced by bacterial endotoxin, at least partly through the inhibition of the enhanced expression of proinflammatory cytokines and chemokines.

Address correspondence to: Dr. Hirohisa Takano, Inhalation Toxicology and Pathophysiology Research Team, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan. E-mail: htakano{at}nies.go.jp

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]