The Role of Human Neutrophil Elastase and Its Inhibitor Elafin in Ulcerative Colitis

K.KOK; CURCIARELLO R; P. BIANCHERI; L.LANGMEAD; T.MACDONALD

Vancouver, BC

Congreso; 16th International Congress of Mucosal Immunology; 2013

Society of Mucosal Immunology

Background: In ulcerative colitis (UC) neutrophils infiltrating the inflamed mucosa release humanneutrophil elastase (HNE), causing matrix degradation, as well as its specific inhibitor, elafin. We aimed toevaluate elastase and elafin production in active UC, and to investigate the modulatory effect of elafin onmucosal proteolytic activity. Methods: Intestinal biopsies from patients with active UC (18) and healthycontrols (12) were homogenised and analysed for proteolytic activity and elafin concentration (ELISA).The in vitro effect of different protease inhibitors (elafin, marimastat, AAVP) on proteolytic activity ofmucosal homogenates was determined. Biopsies from inflamed UC mucosa were cultured ex vivo for 24hours with or without elafin and the effect on proteolytic activity was evaluated. Results: Mucosal samplesfrom patients with active UC display significantly higher proteolytic activity and elafin levels than healthycontrols. The in vitro addition of elafin, marimastat and AAVP significantly diminishes proteolytic activity.Elafin reduces proteolytic activity of inflamed UC biopsies cultured ex vivo. Conclusion: Colonic mucosafrom UC patients show higher elastinolytic activity compared with healthy controls. Elafin has a restorativeeffect on the elastinolytic activity of UC mucosal homogenates. We observe a beneficial modulatory effectof elafin on human gut tissue, suggesting a possible therapeutic role of elafin in UC.