Surfactant Protein D Dampens Lung Injury by Suppressing NLRP3 Inflammasome Activation and NF-κB Signaling in Acute Pancreatitis.

Abstract

Wild-type C57BL/6 (WT), SP-D knockout (KO), and humanized transgenic SP-D (hTG) mice were used in this study. SAP was induced by administration of one-dose lipopolysaccharide (10 mg/kg) and 6 hourly intraperitoneal injections of cerulein (Cn) (100 μg/kg). Animals were killed 6 and 24 h after first Cn treatment. Histopathologic changes in pancreas and lung were assessed by light and electron microscopes. Serum amylase, IL-1β, IL-6, and MCP-1 levels were determined by kit/ELISA. NLRP3 inflammasome, NF-κB, and MPO activations were analyzed by western blotting and immunofluorescence. KO mice showed more severe pancreatic and lung injury than WT mice in SAP. hTG mice exhibited similar degree in lung injury as WT mice. Mitochondrial and rough endoplasmic reticulum damages, autophagosome formation were observed in the alveolar type II and acinar cells of SAP mice. SAP KO mice had increased bronchoalveolar lavage fluid inflammatory cells, higher levels of serum IL-1β, IL-6, and MCP-1 than SAP WT and hTG mice. Levels of NLRP3 inflammasome (NLRP3, ASC, and Caspase-1) and NF-κB activation in SAP KO mice were higher than SAP WT and hTG mice. SP-D exerts protective effects against ALI via suppressing NLRP3 inflammasome and NF-κB activation in experimental SAP.