VMP1-mediated autophagy in pancreatic acinar cell prevents inflammatory damaged in experimental acute pancreatitis

BOGGIO, V.; TORASSO, L.; ALEJANDRO JAVIER ROPOLO; VACCARO, M. I.

Simposio; WIA Annual Symposium 2022; 2022

Women in Autophagy

Acute pancreatitis (AP) is a local inflammation that in severe presentation induces SIRS triggering organ failure. During AP, monocytes and neutrophils activated through NLRP3-inflammasome receptor infiltrate pancreas. Autophagy regulates inflammasome removing NLRP3 components, activators and cytokines. In transgenic mice expressing VMP1 in acinar cells (VMP1-Ela1) developing spontaneous autophagy, we characterized zymophagy that prevents acinar cell death in AP. We investigate extrapancreatic organ failure in VMP1-Ela1 and wilt type (WT) mice inducing severe AP by supramaximal cerulein plus enterokinase (CAE+EK) treatment. VMP1-Ela1 only presented interlobular edema while in WT mice CAE+EK treatment induced pancreatic edema, necrosis and hemorrhage characteristic of AP. Serum amylase and lipase were significantly reduced in VMP1-Ela1 comparing to WT mice. Regardless extrapancreatic organ failure, lung?s histology of WT mice showed dramatical increased septal thickness and hemorrhagic foci within alveolar spaces. In contrast, Ela1-VMP1 mice showed normal lung tissue. Moreover, kidney?s histoarchitecture was preserved in VMP1-Ela1 while in WT mice CAE+EK treatment induced acute tubular necrosis. These results suggest that VMP1-mediated autophagy could be modulating the inflammatory process. Finally, to assess if VMP1 is implicated in inflammasome activation modulating SIRS in severe AP we used monocyte cell lines activated with a LPS as a model. We worked with THP-1 and THP-1-ASC-GFP cells activated by LPS+ATP. We found that NLRP3-inflammasome activation increased VMP1 expression and IL-1 production analyzed by western blot and ASC-GFP expression by fluorescence microscopy. Considering all these results suggest that VMP1-mediated autophagy during acute pancreatitis reduces complications of inflammation probably by regulating NLRP3-inflammasome activation.