Urinary trypsin inhibitor as a therapeutic option for endotoxin-related inflammatory disorders.
BACKGROUND
Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used as a drug for patients with inflammatory disorders such as pancreatitis, shock and disseminated intravascular coagulation (DIC). Previous in vitro studies have demonstrated that serine protease inhibitors may have anti-inflammatory properties at sites of inflammation. However, the therapeutic effects of UTI in vivo remain unclarified, as commercial UTI has been developed to act against humans, with the activity and selectivity toward the relevant animal UTI being less characterized.


METHODS
In this review, we introduce the roles of UTI in experimental endotoxin (lipopolysaccharide; LPS)-related inflammatory disorders using UTI-deficient (-/-) and corresponding wild-type mice.


RESULTS
Our experiments using genetic approach suggest that endogenous UTI can protect against the systemic inflammatory response and subsequent organ injury induced by LPS, at least partly, through the inhibition of pro-inflammatory cytokine and chemokine expression, which provide important in vivo evidence and understanding about a protective role of UTI in inflammatory conditions.


CONCLUSIONS
Using genetically targeted mice selectively lacking UTI, UTI has been evidenced to provide an attractive 'rescue' therapeutic option for endotoxin-related inflammatory disorders such as DIC, acute lung injury and acute liver injury.
Inoue
Ken-ichiro
K
National Institute for Environmental Studies, Environmental Health Sciences Division, 16-2 Onogawa, Tsukuba 305-8506, Japan. inoue.kenichirou@nies.go.jp
Takano
Hirohisa
H
D055371:Acute Lung Injury / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000009:adverse effects / Q000633:toxicity; D006023:Glycoproteins / Q000172:deficiency / Q000502:physiology / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000009:adverse effects / Q000627:therapeutic use* / Q000633:toxicity; D017114:Liver Failure, Acute / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012772:Shock, Septic / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*
D004731:Endotoxins; D006023:Glycoproteins; D018836:Inflammation Mediators; C028665:urinastatin