Legumain is activated in macrophages during pancreatitis Journal Article

Authors: Edgington-Mitchell, L. E.; Wartmann, T.; Fleming, A. K.; Gocheva, V.; van der Linden, W. A.; Withana, N. P.; Verdoes, M.; Aurelio, L.; Edgington-Mitchell, D.; Lieu, T.; Parker, B. S.; Graham, B.; Reinheckel, T.; Furness, J. B.; Joyce, J. A.; Storz, P.; Halangk, W.; Bogyo, M.; Bunnett, N. W.
Article Title: Legumain is activated in macrophages during pancreatitis
Abstract: Pancre-atitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked to inflammatory diseases such as atherosclerosis, stroke, and cancer. Until now, legumain activation has not been studied during pancreatitis. We used a fluorescently quenched activity-based probe to assess legumain activation during caerulein-induced pancreatitis in mice. We detected activated legumain by ex vivo imaging, confocal microscopy, and gel electrophoresis. Compared with healthy controls, legumain activity in the pancreas of caeruleintreated mice was increased in a time-dependent manner. Legumain was localized to CD68+ macrophages and was not active in pancreatic acinar cells. Using a small-molecule inhibitor of legumain, we found that this protease is not essential for the initiation of pancreatitis. However, it may serve as a biomarker of disease, since patients with chronic pancreatitis show strongly increased legumain expression in macrophages. Moreover, the occurrence of legumain-expressing macrophages in regions of acinar-to-ductal metaplasia suggests that this protease may influence reprogramming events that lead to inflammation-induced pancreatic cancer. © 2016 the American Physiological Society.
Keywords: pancreas; inflammation; biomarker; pancreatitis; pancreatic cancer; macrophage; cysteine cathepsin; activity-based probe; legumain
Journal Title: American Journal of Physiology - Gastrointestinal and Liver Physiology
Volume: 311
Issue: 3
ISSN: 0193-1857
Publisher: American Physiological Society  
Date Published: 2016-09-01
Start Page: G548
End Page: G560
Language: English
DOI: 10.1152/ajpgi.00047.2016
PROVIDER: scopus
PUBMED: 27514475
PMCID: PMC5075999
Notes: Article -- Export Date: 3 October 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Johanna A Joyce
    67 Joyce
  2. Vasilena Gocheva
    15 Gocheva