Skip to main content
Top
Published in: Digestive Diseases and Sciences 12/2018

01-12-2018 | Original Article

Resolvin D1 Resolve Inflammation in Experimental Acute Pancreatitis by Restoring Autophagic Flux

Authors: Bingbing Wang, Cui Hu, Yongyu Mei, Junjun Bao, Shaozhen Ding, Xiaochang Liu, Qiao Mei, Jianming Xu

Published in: Digestive Diseases and Sciences | Issue 12/2018

Login to get access

Abstract

Background

Acute pancreatitis (AP) is a common acute gastrointestinal disorders. Increasing evidence indicated that autophagy is involved in the development of AP. Resolvin D1 is an endogenous pro-resolving lipid mediator, which can protect mice from cerulein-induced acute pancreatitis and facilitate autophagy in macrophage, but its mechanism remians unclear.

Aims

To investigate the effect of resolvin D1 on autophagy in mouse models of cerulein-induced AP.

Methods

C57BL/6 mice were randomly divided into control group, AP group and resolvin D1 group. The models of cerulein-induced AP were constructed by intraperitoneally cerulein. Resolvin D1 group was established by intraperitoneally resolvin D1 based on AP models, simultaneously, control group received normal saline. The severity of AP, the level of inflammatory cytokines, the number of autophagic vacuoles, and the expression of autophagy-related markers were evaluated among three groups.

Results

The AP models were established successfully. Compared to control group, the number of autophagic vacuoles and expressions of autophagy-related markers including Beclin-1, p62 and LC3-II were increased in AP models, In contrast, the degree of inflammation and levels of inflammatory cytokines in AP models were reduced after resolvin D1 treatment. Moreover, resolvin D1 attenuated the number of autophagic vacuoles and expressions of autophagy-related markers.

Conclusions

Autophagic flux is impaired in cerulein-induced AP. Resolvin D1 ameliorate the severity of mice with cerulein-induced acute pancreatitis, possible attributing to its reducing impaired autophagy and restoring autophagic flux.
Literature
1.
go back to reference Xiao AY, Tan MLY, Wu LM, et al. Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol. 2016;1:45–55.CrossRef Xiao AY, Tan MLY, Wu LM, et al. Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol. 2016;1:45–55.CrossRef
2.
go back to reference Singh P, Garg PK. Pathophysiological mechanisms in acute pancreatitis: current understanding. Indian J Gastroenterol. 2016;35:153–166.CrossRef Singh P, Garg PK. Pathophysiological mechanisms in acute pancreatitis: current understanding. Indian J Gastroenterol. 2016;35:153–166.CrossRef
3.
go back to reference Hashimoto D, Ohmuraya M, Hirota M, et al. Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells. J Cell Biol. 2008;181:1065–1072.CrossRef Hashimoto D, Ohmuraya M, Hirota M, et al. Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells. J Cell Biol. 2008;181:1065–1072.CrossRef
4.
go back to reference Mareninova OA, Hermann K, French SW, et al. Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis. J Clin Investig. 2009;119:3340.PubMed Mareninova OA, Hermann K, French SW, et al. Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis. J Clin Investig. 2009;119:3340.PubMed
5.
go back to reference Gukovsky I, Li N, Todoric J, et al. Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer. Gastroenterology. 2013;144:1199–1209.CrossRef Gukovsky I, Li N, Todoric J, et al. Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer. Gastroenterology. 2013;144:1199–1209.CrossRef
6.
go back to reference Chinzei R, Masuda A, Nishiumi S, et al. Vitamin K3 attenuates cerulein-induced acute pancreatitis through inhibition of the autophagic pathway. Pancreas. 2011;40:84–94.CrossRef Chinzei R, Masuda A, Nishiumi S, et al. Vitamin K3 attenuates cerulein-induced acute pancreatitis through inhibition of the autophagic pathway. Pancreas. 2011;40:84–94.CrossRef
7.
go back to reference Xiao J, Feng X, Huang XY, et al. Spautin-1 ameliorates acute pancreatitis via inhibiting impaired autophagy and alleviating calcium overload. Mol Med. 2016;22:643.CrossRef Xiao J, Feng X, Huang XY, et al. Spautin-1 ameliorates acute pancreatitis via inhibiting impaired autophagy and alleviating calcium overload. Mol Med. 2016;22:643.CrossRef
8.
go back to reference Feng Y, He D, Yao Z, et al. The machinery of macroautophagy. Cell Res. 2014;24:24.CrossRef Feng Y, He D, Yao Z, et al. The machinery of macroautophagy. Cell Res. 2014;24:24.CrossRef
9.
go back to reference Mizushima N, Levine B, Cuervo AM, et al. Autophagy fights disease through cellular self-digestion. Nature. 2008;451:1069.CrossRef Mizushima N, Levine B, Cuervo AM, et al. Autophagy fights disease through cellular self-digestion. Nature. 2008;451:1069.CrossRef
10.
go back to reference Hale AN, Ledbetter DJ, Gawriluk TR, et al. Autophagy: regulation and role in development. Autophagy. 2013;9:951–972.CrossRef Hale AN, Ledbetter DJ, Gawriluk TR, et al. Autophagy: regulation and role in development. Autophagy. 2013;9:951–972.CrossRef
11.
go back to reference Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science. 2004;306:990–995.CrossRef Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science. 2004;306:990–995.CrossRef
12.
go back to reference Antonucci L, Fagman JB, Kim JY, et al. Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress. Proc Natl Acad Sci USA. 2015;112:E6166–E6174.CrossRef Antonucci L, Fagman JB, Kim JY, et al. Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress. Proc Natl Acad Sci USA. 2015;112:E6166–E6174.CrossRef
13.
go back to reference Krishnamoorthy S, Recchiuti A, Chiang N, et al. Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci USA. 2010;107:1660–1665.CrossRef Krishnamoorthy S, Recchiuti A, Chiang N, et al. Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci USA. 2010;107:1660–1665.CrossRef
14.
go back to reference Zhao X, Bao J, Hu C, et al. Effect of diclofenac on the levels of lipoxin A4 and Resolvin D1 and E1 in the post-ERCP pancreatitis. Dig Dis Sci. 2014;59:2992–2996.CrossRef Zhao X, Bao J, Hu C, et al. Effect of diclofenac on the levels of lipoxin A4 and Resolvin D1 and E1 in the post-ERCP pancreatitis. Dig Dis Sci. 2014;59:2992–2996.CrossRef
15.
go back to reference Liu Y, Zhou D, Long FW, et al. Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury. Am J Physiol Gastrointest Liver Physiol. 2016;310:G303–G309.CrossRef Liu Y, Zhou D, Long FW, et al. Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury. Am J Physiol Gastrointest Liver Physiol. 2016;310:G303–G309.CrossRef
16.
go back to reference Prieto P, Rosales-Mendoza CE, Terrón V, et al. Activation of autophagy in macrophages by pro-resolving lipid mediators. Autophagy. 2015;11:1729–1744.CrossRef Prieto P, Rosales-Mendoza CE, Terrón V, et al. Activation of autophagy in macrophages by pro-resolving lipid mediators. Autophagy. 2015;11:1729–1744.CrossRef
17.
go back to reference Schmidt J, Lewandrowski K, Fernandez-del Castillo C, et al. Histopathologic correlates of serum amylase activity in acute experimental pancreatitis. Dig Dis Sci. 1992;37:1426–1433.CrossRef Schmidt J, Lewandrowski K, Fernandez-del Castillo C, et al. Histopathologic correlates of serum amylase activity in acute experimental pancreatitis. Dig Dis Sci. 1992;37:1426–1433.CrossRef
18.
go back to reference Imanaka H, Shimaoka M, Matsuura N, et al. Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-β1 mRNA upregulation in rat lungs. Anesth Analg. 2001;92:428–436.CrossRef Imanaka H, Shimaoka M, Matsuura N, et al. Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-β1 mRNA upregulation in rat lungs. Anesth Analg. 2001;92:428–436.CrossRef
19.
go back to reference Dambrauskas Z, Giese N, Gulbinas A, et al. Different profiles of cytokine expression during mild and severe acute pancreatitis. World J Gastroenterol. 2010;16:1845.CrossRef Dambrauskas Z, Giese N, Gulbinas A, et al. Different profiles of cytokine expression during mild and severe acute pancreatitis. World J Gastroenterol. 2010;16:1845.CrossRef
20.
go back to reference Takahashi K, Mashima H, Miura K, et al. Disruption of small GTPase Rab7 exacerbates the severity of acute pancreatitis in experimental mouse models. Sci Rep (UK). 2017;7:2817.CrossRef Takahashi K, Mashima H, Miura K, et al. Disruption of small GTPase Rab7 exacerbates the severity of acute pancreatitis in experimental mouse models. Sci Rep (UK). 2017;7:2817.CrossRef
21.
go back to reference Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2016;12:1–222.CrossRef Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2016;12:1–222.CrossRef
22.
go back to reference Gukovskaya AS, Gukovsky I. Autophagy and pancreatitis. AJP Gastrointest Liver Physiol. 2012;303:G993–G1003.CrossRef Gukovskaya AS, Gukovsky I. Autophagy and pancreatitis. AJP Gastrointest Liver Physiol. 2012;303:G993–G1003.CrossRef
23.
go back to reference Mofidi R, Duff MD, Wigmore SJ, et al. Association between early systemic inflammatory response, severity of multiorgan dysfunction and death in acute pancreatitis. Br J Surg. 2006;93:738–744.CrossRef Mofidi R, Duff MD, Wigmore SJ, et al. Association between early systemic inflammatory response, severity of multiorgan dysfunction and death in acute pancreatitis. Br J Surg. 2006;93:738–744.CrossRef
24.
go back to reference Fortunato F, Kroemer G. Impaired autophagosome-lysosome fusion in the pathogenesis of pancreatitis. Autophagy. 2009;5:850–853.CrossRef Fortunato F, Kroemer G. Impaired autophagosome-lysosome fusion in the pathogenesis of pancreatitis. Autophagy. 2009;5:850–853.CrossRef
25.
26.
go back to reference Xu B, Bai B, Sha S, et al. Interleukin-1β induces autophagy by affecting calcium homeostasis and trypsinogen activation in pancreatic acinar cells. Int J Clin Exp Med. 2014;7:3620. Xu B, Bai B, Sha S, et al. Interleukin-1β induces autophagy by affecting calcium homeostasis and trypsinogen activation in pancreatic acinar cells. Int J Clin Exp Med. 2014;7:3620.
27.
go back to reference Mareninova OA, Sendler M, Malla SR, et al. Lysosome-associated membrane proteins (LAMP) maintain pancreatic acinar cell homeostasis: LAMP-2–deficient mice develop pancreatitis. Cell Mol Gastroenterol Hepatol. 2015;1:678–694.CrossRef Mareninova OA, Sendler M, Malla SR, et al. Lysosome-associated membrane proteins (LAMP) maintain pancreatic acinar cell homeostasis: LAMP-2–deficient mice develop pancreatitis. Cell Mol Gastroenterol Hepatol. 2015;1:678–694.CrossRef
28.
go back to reference Cao Y, Yang W, Tyler MA, et al. Noggin attenuates cerulein-induced acute pancreatitis and the impaired autophagy. Pancreas. 2013;42:301.CrossRef Cao Y, Yang W, Tyler MA, et al. Noggin attenuates cerulein-induced acute pancreatitis and the impaired autophagy. Pancreas. 2013;42:301.CrossRef
Metadata
Title
Resolvin D1 Resolve Inflammation in Experimental Acute Pancreatitis by Restoring Autophagic Flux
Authors
Bingbing Wang
Cui Hu
Yongyu Mei
Junjun Bao
Shaozhen Ding
Xiaochang Liu
Qiao Mei
Jianming Xu
Publication date
01-12-2018
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 12/2018
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-018-5191-4

Other articles of this Issue 12/2018

Digestive Diseases and Sciences 12/2018 Go to the issue