期刊
SHOCK
卷 51, 期 5, 页码 557-568出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SHK.0000000000001244
关键词
Acute lung injury (ALI); acute pancreatitis (AP); NF-kappa B signaling; NLRP3 inflammasome; surfactant protein D (SP-D)
资金
- NIH [R01HL136706]
- NSF [1722630]
- National Natural Science Foundation of China [81300356]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL136706] Funding Source: NIH RePORTER
Severe acute pancreatitis (SAP) often causes acute lung injury (ALI) by systemic inflammatory response. Surfactant protein D (SP-D) plays critical roles in host defense and inflammation regulation. NLRP3 inflammasomes and NF-kappa B signaling are key regulators in innate immunity and inflammation. We hypothesized that SP-D attenuates ALI by suppressing NLRP3 inflammasome and NF-kappa B activation. Methods: 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) (100mg/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-1 beta, IL-6, and MCP-1 levels were determined by kit/ELISA. NLRP3 inflammasome, NF-kappa B, and MPO activations were analyzed by western blotting and immunofluorescence. Results: KO mice showed more severe pancreatic and lung injury than WTmice in SAP. hTG mice exhibited similar degree in lung injury as WTmice. Mitochondrial and rough endoplasmic reticulum damages, autophagosome formation were observed in the alveolar type II and acinar cells of SAP mice. SAP KOmice had increased bronchoalveolar lavage fluid inflammatory cells, higher levels of serum IL-1 beta, IL-6, and MCP-1 than SAP WT and hTG mice. Levels of NLRP3 inflammasome (NLRP3, ASC, and Caspase-1) and NF-kappa B activation in SAP KOmice were higher than SAPWTand hTGmice. Conclusion: SP-D exerts protective effects against ALI via suppressing NLRP3 inflammasome and NF-kappa B activation in experimental SAP.
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