title: Urinary trypsin inhibitor reduces C-X-C chemokine production in rat liver ischemia/reperfusion.
abstract: OBJECTIVE
  Protease inhibitors attenuate ischemia/reperfusion injury. However, the underlying mechanisms by which protease inhibitors prevent reperfusion injury remain obscure. Neutrophils play an important role in reperfusion injury. We studied the effects of urinary trypsin inhibitor (UTI) on production of the C-X-C chemokine, cytokine-induced neutrophil chemoattractant (CINC), by Kupffer cells during ischemia/reperfusion of the liver.
  
  
  METHODS
  Liver ischemia was induced in rats by occlusion of the portal vein for 30 min. UTI (50,000 U/kg) was injected intravenously 5 min before vascular clamping. Serum CINC concentrations were measured by enzyme-linked immunosorbent assay. Levels of CINC mRNA in the liver were determined by Northern blot analysis. We also examined the inhibitory effects of UTI on in vitro CINC production by peritoneal macrophages in response to neutrophil elastase (NE).
  
  
  RESULTS
  Serum CINC concentrations increased and peaked 6 h after reperfusion. However, pretreatment of animals with UTI blunted this increase in CINC and significantly reduced CINC mRNA levels in the liver after ischemia/reperfusion. UTI also decreased neutrophil accumulation in the liver 24 h after reperfusion. In vitro CINC production by Kupffer cells from rats pretreated with UTI 3 h after ischemia/reperfusion was significantly decreased compared to those from untreated animals. UTI reduced NE activity in vitro in a dose-dependent manner, and UTI significantly reduced in vitro CINC production by peritoneal macrophages stimulated with NE.
  
  
  CONCLUSIONS
  UTI reduces the production of CINC by Kupffer cells stimulated with NE, attenuating ischemia/reperfusion injury of the liver.
authors: Department of Surgery II, Kumamoto University Medical School, Kumamoto, Japan.
authors: Y
authors: Y
authors: Yamaguchi
authors: H
authors: H
authors: Ohshiro
authors: Y
authors: Y
authors: Nagao
authors: K
authors: K
authors: Odawara
authors: K
authors: K
authors: Okabe
authors: H
authors: H
authors: Hidaka
authors: K
authors: K
authors: Ishihara
authors: S
authors: S
authors: Uchino
authors: T
authors: T
authors: Furuhashi
authors: S
authors: S
authors: Yamada
authors: K
authors: K
authors: Mori
authors: M
authors: M
authors: Ogawa
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000235:genetics*; D002630:Chemotactic Factors / Q000097:blood / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D006133:Growth Substances / Q000097:blood / Q000235:genetics*; D006801:Humans; D007275:Injections, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology*; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000098:blood supply* / Q000276:immunology / Q000503:physiopathology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D011169:Portal Vein; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D014158:Transcription, Genetic / Q000187:drug effects; D014361:Trypsin Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007976:Leupeptins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D019272:Leukocyte Elastase; C028665:urinastatin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde