Legumain is activated in macrophages during pancreatitis

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 controls, legumain activity in the pancreas of caerulein-treated 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.

Transcriptome profiling of antiviral immune and dietary fatty acid dependent responses of Atlantic salmon macrophage-like cells

“…up-regulated in pIC group of FO5 at 24 HPS); however, qPCR showed that the expression of this transcript significantly increased in the pIC group of FO5 at 6 HPS compared to that of FO7. lgmn is associated with macrophage activity and differentiation in mammals [ 61 , 62 ], and it has been shown to be more highly expressed in mature macrophages compared with less differentiated stages (early progenitors and monocytes) in goldfish [ 63 ]. If lgmn function is conserved in mammalian and teleost macrophages, then our lgmn expression results suggest that dietary fish oil (i.e.…”

Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions

“…The potential role and limitations of legumain as a biomarker was discussed in an editorial in the same issue of Atherosclerosis [282] as paper II. Legumain has also been suggested as biomarker for liver fibrosis [283] and pancreatitis [284]. A biomarker is defined as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, or pharmacological responses to a therapeutic intervention" [285].…”

Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication

“…In pancreatic cancer, it was noted that AEP exists in exosomes and that AEP-harboring exosomes potentiate phosphoinositide 3-kinase (PI3K) signaling pathways, causing enhanced invasion ability of exosome-receiving cells [38] (Figure 1 and Table 1). Intriguingly, patients with chronic pancreatitis, one of the causes of pancreatic cancer, show the high levels of AEP in macrophages [39]. Furthermore, AEP is detected in stroma and endothelial cells in pancreatic cancer tissues [40].…”