Autophagy, Inflammation, and Immune Dysfunction in the Pathogenesis of Pancreatitis

Gastroenterology. 2017 Nov;153(5):1212-1226. doi: 10.1053/j.gastro.2017.08.071. Epub 2017 Sep 14.

Abstract

Pancreatitis is a common disorder with significant morbidity and mortality, yet little is known about its pathogenesis, and there is no specific or effective treatment. Its development involves dysregulated autophagy and unresolved inflammation, demonstrated by studies in genetic and experimental mouse models. Disease severity depends on whether the inflammatory response resolves or amplifies, leading to multi-organ failure. Dysregulated autophagy might promote the inflammatory response in the pancreas. We discuss the roles of autophagy and inflammation in pancreatitis, mechanisms of deregulation, and connections among disordered pathways. We identify gaps in our knowledge and delineate perspective directions for research. Elucidation of pathogenic mechanisms could lead to new targets for treating or reducing the severity of pancreatitis.

Keywords: Cytokine; Lysosome; Macrophage; Mitochondrial Dysfunction.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Humans
  • Inflammation Mediators / immunology*
  • Inflammation Mediators / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Pancreas / immunology*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatitis / immunology*
  • Pancreatitis / metabolism
  • Pancreatitis / pathology
  • Prognosis
  • Severity of Illness Index
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Cytokines
  • Inflammation Mediators