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From endoplasmic-reticulum stress to the inflammatory response

Nature volume 454, pages 455–462 (2008)Cite this article

Abstract

The endoplasmic reticulum is responsible for much of a cell's protein synthesis and folding, but it also has an important role in sensing cellular stress. Recently, it has been shown that the endoplasmic reticulum mediates a specific set of intracellular signalling pathways in response to the accumulation of unfolded or misfolded proteins, and these pathways are collectively known as the unfolded-protein response. New observations suggest that the unfolded-protein response can initiate inflammation, and the coupling of these responses in specialized cells and tissues is now thought to be fundamental in the pathogenesis of inflammatory diseases. The knowledge gained from this emerging field will aid in the development of therapies for modulating cellular stress and inflammation.

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Figure 1: The mammalian UPR pathways.
Figure 2: Oxidative protein folding.
Figure 3: Proposed models for UPR-mediated JNK and NF-κB activation.
Figure 4: The ER-stress-induced acute-phase response.
Figure 5: The role of calcium and ROS in the UPR and inflammation.
Figure 6: The 'ER-stress–inflammation' loop in specialized cells.

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Acknowledgements

We thank J. Mitchell for her efforts in preparing the manuscript. We apologize to those whose work could not be cited because of space limitations. K.Z. is supported by a grant from the American Heart Association (0635423Z). R.J.K. is supported by grants from the National Institutes of Health (DK042394, HL052173 and HL057346) and is an investigator of the Howard Hughes Medical Institute.

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  1. Kezhong Zhang

    Present address: Present address: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, Michigan 48201, USA.,

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  1. Department of Biological Chemistry, The University of Michigan Medical Center, 1150 West Medical Center Drive, Ann Arbor, 48109, Michigan, USA

    Kezhong Zhang & Randal J. Kaufman

  2. Department of Internal Medicine, The University of Michigan Medical Center, 1150 West Medical Center Drive, Ann Arbor, 48109, Michigan, USA

    Randal J. Kaufman

  3. Howard Hughes Medical Institute, The University of Michigan Medical Center, 1150 West Medical Center Drive, Ann Arbor, 48109, Michigan, USA

    Randal J. Kaufman

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Correspondence should be addressed to R.J.K. (kaufmanr@umich.edu).

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Zhang, K., Kaufman, R. From endoplasmic-reticulum stress to the inflammatory response. Nature 454, 455–462 (2008). https://doi.org/10.1038/nature07203

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