Exosomes Derived From Cerulein-Induced Pancreatic Acinar Cells Mediate Peritoneal Macrophage M1 Polarization and Pyroptosis via a BIRC3/NLRC4 Axis in Acute Pancreatitis.

Acute pancreatitis (AP) is a frequent exocrine inflammation of the pancreas that causes severe abdominal pain and multiorgan dysfunction that may lead to pancreatic necrosis and persistent organ failure. Previous studies have indicated that the pathogenesis of AP is based on the Cerulein-triggered experimental model, which simulates human AP in vivo. As reported, pancreatic acinar cells and peritoneal macrophages partake in pancreatic inflammation and injury. Nevertheless, the association between them is poorly understood. NLRC4 was highly expressed, and BIRC3 was reduced in AP patients and Cerulein-treated AR42J cells. Exosomes derived from Cerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis, which were partly abolished by NLRC4 silencing. Moreover, BIRC3 triggered the ubiquitination of NLRC4 and promoted its degradation. Besides, exosomal BIRC3 repressed sodium taurocholate-induced pancreatic lesions in vivo. Exosomes derived from Cerulein-stimulated pancreatic acinar cells promote peritoneal macrophage M1 polarization and pyroptosis by a BIRC3/NLRC4 axis in AP, providing a promising strategy to protect against AP.