Methylprednisolone Protects Severe Acute Pancreatitis And Pancreatitis-Associated Acute Lung Injury in Mice By Inhibiting NLRP3 Inflammasome Through NF-?B

Abstract

Chao He, Chuan-jiang Liu, Qiang Fu, Pan Liu, Peng Xia, Xu Zhang, Rui Chen, Zhen-sheng Zhai, Yu-zhu Wang, Tao Qin, Wenjing Zhou, Hong-wei Zhang

In serve acute pancreatitis (SAP), the rapid production and releasing of inflammatory cytokines can cause local and systemic excessive inflammation, especially pancreatitis-associated acute lung injury (P-ALI). Methylprednisolone (MP) is a synthetic corticosteroid with potent anti-inflammatory and antioxidant properties used as therapy for a variety of diseases. In this study, we found MP, used in the early phase of SAP, decreased the levels of IL-1β and TNF-α in serum and peritoneal lavage fluids (PLF), reduced the level of serum amylase and the expression of MPO in lung tissue, attenuated the pathological injury of the pancreas and lungs in a dosedependent manner. The expression of NLRP3 and IL-1β in pancreas and lungs was down regulated significantly depending on the MP concentration. In vitro, MP reduced the levels of IL-1β and TNF-α by down regulating the expression of NLRP3, IL-1β and p-NF-κB in isolated peritoneal macrophages. Taken together, MP can attenuate the injury of pancreas and lungs, and the inflammatory response in SAP mice by down regulating the activation of NF-κB and the NLRP3 inflammasome.

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