Open AccessNLRP3 Deficiency Alleviates Severe Acute Pancreatitis and Pancreatitis-Associated Lung Injury in a Mouse Model
Author(s) -
Qiang Fu,
Zhensheng Zhai,
Yuzhu Wang,
Lixia Xu,
Pengchong Jia,
Peng Xia,
Chuanjiang Liu,
Xu Zhang,
Tao Qin,
Hongwei Zhang
Publication year - 2018
Publication title -
biomed research international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 126
eISSN - 2314-6141
pISSN - 2314-6133
DOI - 10.1155/2018/1294951
Subject(s) - pancreatitis , acute pancreatitis , medicine , lung , pulmonary injury , intensive care medicine , gastroenterology , pathology , pulmonary fibrosis
The rapid production and release of a large number of inflammatory cytokines can cause excessive local and systemic inflammation in severe acute pancreatitis (SAP) and multiple organ dysfunction syndrome (MODS), especially pancreatitis-associated acute lung injury (P-ALI), which is the main cause of early death in patients with SAP. The NLRP3 inflammasome plays an important role in the maturation of IL-1 β and the inflammatory cascade. Here, we established a model of SAP using wild-type (NLRP3 +/+ ) and NLRP3 knockout (NLRP3 −/− ) mice by intraperitoneal injections of caerulein (Cae) and lipopolysaccharide (LPS). Pathological injury to the pancreas and lungs, the inflammatory response, and neutrophil infiltration were significantly mitigated in NLRP3 −/− mice. Furthermore, INF-39, an NLRP3 inflammasome inhibitor, could reduce the severity of SAP and P-ALI in a dose-dependent manner. Our results suggested that SAP and P-ALI were alleviated by NLRP3 deficiency in mice, and thus, reducing NLRP3 expression may mitigate SAP-associated inflammation and P-ALI.