Journal article

Legumain is activated in macrophages during pancreatitis

Laura E Edgington-Mitchell, Thomas Wartmann, Alicia K Fleming, Vasilena Gocheva, Wouter A van der Linden, Nimali P Withana, Martijn Verdoes, Luigi Aurelio, Daniel Edgington-Mitchell, TinaMarie Lieu, Belinda S Parker, Bim Graham, Thomas Reinheckel, John B Furness, Johanna A Joyce, Peter Storz, Walter Halangk, Matthew Bogyo, Nigel W Bunnett

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | AMER PHYSIOLOGICAL SOC | Published : 2016

Abstract

Pancreatitis 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 contro..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by National Institutes of Health


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING


Funding Acknowledgements

L. E. Edgington-Mitchell is supported by National Health and Medical Research Council (NHMRC) Early Career Fellowship Grant GNT1091636. N. W. Bunnett is supported by NHMRC and the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology. This work was supported in part by grants from the National Institutes of Health Grants R01-EB-005011 (to M. Bogyo) and R01-CA-200572 (to P. Storz).