Inflammation and cellular stress: a mechanistic link between immune-mediated and metabolically driven pathologies

Eur J Nutr. 2011 Jun;50(4):219-33. doi: 10.1007/s00394-011-0197-0. Epub 2011 May 1.

Abstract

Background: Multiple cellular stress responses have been implicated in chronic diseases such as obesity, diabetes, cardiovascular, and inflammatory bowel diseases. Even though phenotypically different, chronic diseases share cellular stress signaling pathways, in particular endoplasmic reticulum (ER) unfolded protein response (UPR).

Results and methods: The purpose of the ER UPR is to restore ER homeostasis after challenges of the ER function. Among the triggers of ER UPR are changes in the redox status, elevated protein synthesis, accumulation of unfolded or misfolded proteins, energy deficiency and glucose deprivation, cholesterol depletion, and microbial signals. Numerous mouse models have been used to characterize the contribution of ER UPR to several pathologies, and ER UPR-associated signaling has also been demonstrated to be relevant in humans. Additionally, recent evidence suggests that the ER UPR is interrelated with metabolic and inflammatory pathways, autophagy, apoptosis, and mitochondrial stress signaling. Furthermore, microbial as well as nutrient sensing is integrated into the ER-associated signaling network.

Conclusion: The data discussed in the present review highlight the interaction of ER UPR with inflammatory pathways, metabolic processes and mitochondrial function, and their interrelation in the context of chronic diseases.

Publication types

  • Review

MeSH terms

  • Activating Transcription Factor 6 / metabolism
  • Animals
  • Autophagy
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / metabolism*
  • Endoribonucleases / metabolism
  • Homeostasis
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism*
  • Metabolic Diseases / drug therapy
  • Metabolic Diseases / immunology
  • Metabolic Diseases / metabolism*
  • Mitochondria / metabolism
  • Molecular Targeted Therapy
  • Oxidative Stress
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Stress, Physiological*
  • Unfolded Protein Response*
  • eIF-2 Kinase / metabolism

Substances

  • Activating Transcription Factor 6
  • ERN1 protein, human
  • PERK kinase
  • Protein-Serine-Threonine Kinases
  • eIF-2 Kinase
  • Endoribonucleases