Protective effects of maresin 1 against inflammation in experimentally induced acute pancreatitis and related lung injury

Am J Physiol Gastrointest Liver Physiol. 2019 Sep 1;317(3):G333-G341. doi: 10.1152/ajpgi.00078.2019. Epub 2019 May 24.

Abstract

Severe acute pancreatitis (SAP) is an inflammatory disorder that progresses with local and systemic difficulties accompanied by a relatively high mortality rate. In recent years, maresin 1 (MaR1) has been shown to be a macrophage mediator with effective proresolving and anti-inflammatory properties that prevents the occurrence of various inflammatory conditions. The purpose of this study was to investigate the role of MaR1 in SAP and related lung injury. Experimental SAP was induced in mice with a combination of cerulean and lipopolysaccharide. MaR1 was administered 30 min before the primary injection of cerulean. Biochemical markers and histological injury scores were used to evaluate the severity of acute pancreatitis. To determine the degree of inflammation, serum cytokines and myeloperoxidase activity in pancreas and lung tissues were measured. Western blot analysis detected the activation of NF-κB. After MaR1 pretreatment, the activities of amylase, lipase, TNF-α, IL-1β, and IL-6 were decreased in serum, and the myeloperoxidase activity both in pancreas and in lung tissues significantly decreased, whereas the activity of anti-inflammatory cytokine IL-10 in serum was increased. MaR1-pretreated mice reduced the activation of pancreatic NF-κB and decreased the severity of pancreatic and lung-related injuries. These results confirm that MaR1 alleviated inflammation of the pancreas and lung by inhibiting the activity of NF-κB in experimentally induced acute pancreatitis and exerted anti-inflammatory effects. These findings suggest that MaR1 could be a new and useful drug in the treatment of SAP.NEW & NOTEWORTHY These results provided us evidence to confirm that maresin 1 (MaR1) can alleviate inflammation of the pancreas and lung by inhibiting the activity of NF-κB in experimental induced acute pancreatitis and exerts certain anti-inflammatory effects. These findings suggest that MaR1 could be a new and useful drug in the treatment of severe acute pancreatitis.

Keywords: inflammation; macrophage mediators; maresin 1; severe acute pancreatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Docosahexaenoic Acids / pharmacology*
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Lipopolysaccharides / pharmacology
  • Lung Injury / drug therapy*
  • Lung Injury / pathology
  • Male
  • Mice, Inbred C57BL
  • Pancreas / drug effects
  • Pancreas / pathology

Substances

  • 7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid
  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • Docosahexaenoic Acids