Therapeutic potential of human elafin.

Abstract

Elafin is an endogenous human protein composed of an N-terminal transglutaminase substrate motif and a C-terminal WAP (whey acidic protein)-domain with antiproteolytic properties. Elafin is expressed predominantly in epithelial tissue and potently inhibits the neutrophil-derived serine proteases elastase and proteinase-3 by a competitive tight-binding mechanism. Furthermore, it inhibits EVE (endogenous vascular elastase). Studies on several animal models show that antiprotease augmentation with human elafin is an effective strategy in the treatment of inflammatory vascular, systemic and pulmonary diseases and of inflammation triggered by reperfusion injury. This raises the possibility that elafin might be effective in the treatment of a variety of human inflammatory diseases. In a Phase I clinical trial, elafin was well tolerated. Phase II trials are underway to investigate the therapeutic effects of elafin on post-operative inflammation and the clinical consequences of major surgery. Of particular interest is the reduction of post-operative morbidity after oesophagus cancer surgery, coronary artery bypass surgery and kidney transplantation.

• Authors: Lee Shaw, Oliver Wiedow
• Journal: Biochemical Society transactions (Biochem Soc Trans) Vol. 39 Issue 5 Pg. 1450-4 (Oct 2011) ISSN: 1470-8752 [Electronic] England
• PMID: 21936832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Elafin
• Protease Inhibitors
• Serine Proteinase Inhibitors
• Serine Endopeptidases

Topics

• Animals
• Clinical Trials as Topic
• Elafin (genetics, metabolism, therapeutic use)
• Humans
• Inflammation (drug therapy)
• Lung Diseases (drug therapy)
• Protease Inhibitors (therapeutic use)
• Serine Endopeptidases (metabolism)
• Serine Proteinase Inhibitors (therapeutic use)
• Vascular Diseases (drug therapy)